L-theanine is a super amino acid found naturally in tea leaves, especially in green tea. Known for its calming effects, it’s often used to ease everyday life stresses. However, the supplement may not address the root cause of stress or issues with your mitochondria that are contributing to your sleeplessness.

The Benefits of L-Theanine

Some people use L-theanine as a sleep aid to combat their sleepytime struggles. Fans of the supplement may also tell you it makes them feel more awake and alert during the day, calling the little amino acid their brain’s best friend. 

Here are some of the reasons proponents love it so much:

• Better sleep quality: Many people report uninterrupted sleep filled with deep L-theanine dreams that leave them feeling refreshed each morning. 
• Reduced stress and anxiety: People love to drink a cup of tea after a crazy day to ease their mind. Research shows that the L-theanine in tea can boost dopamine and serotonin, which can make you feel more relaxed. 
• Crystal-clear brain power: Battling brain fog? L-theanine could improve your concentration and help you focus. Studies suggest the benefits could be even better when L-theanine is taken with caffeine. This could be especially helpful for those wondering about using L-theanine for ADHD!

L-Theanine Risks and Side Effects

L-theanine can be great when taken in the recommended dosages. Take too much, though, and you may feel a few side effects, from headaches to dizziness or the jitters. 

Even though L-theanine is generally safe, it’s a good idea to check in with your doctor before you start taking it. 

Tackling the Root Cause

While L-theanine can help, does it solve the underlying problem at hand? At Optimal Circadian Health, we believe sleep struggles and brain fog can often be attributed to mitochondrial issues that usually require more than a simple supplement to fix.

Caring for these tiny powerhouses inside your cells is so important for your sleep. Here’s how they can impact your slumber:

• Energy production: These cells need to produce energy while you snooze.
• Melatonin production: Mitochondria can help produce melatonin, which is the hormone known to regulate sleep.
• Neuronal detox: Mitochondria helps detoxify neurons while you rest for the best possible sleep results.

To optimize mitochondrial health and improve your sleep, you may consider making some dietary or lifestyle changes. Foods like berries and leafy greens can boost nutrients such as B vitamins and magnesium in your system, while regular exercise and hydration could also support your mitochondrial function. 

Addressing your mitochondrial health is key to bettering your overall sleep quality. For a deeper dive into how you can do that, read Sleep Apnea Solution: A Natural Way to Sleep CPAP-Free and dig into the additional resources offered by Optimal Circadian Health!

You’re trying to get a good night’s rest, but your body has other plans.

Frustrating, right?

But fear not, we’re here to help.

In this article, we’ll dive into this sleep disorder and how supplements might just be the secret weapon you’ve been missing.

So, buckle up (or should we say, tuck in?) as we answer the big questions:

1. What’s the deal with sleep and why is sleep apnea a party pooper?
2. Can vitamins and minerals really make a difference in sleep health?
3. What are the top supplements for sleep apnea, and what’s the scoop behind them?
4. How does sleep apnea tango with your immune function, and can supplements cut in?
5. What’s the link between sleep apnea, brain health, and supplements?
6. How can you safely integrate supplements into your sleep apnea management plan?

If you’re tired of counting sheep and ready for some real Z’s, read on!

Understanding Sleep and Sleep Apnea

Sleep, it’s like the oil in your body’s engine. Without it, everything starts to grind and stutter (Chattu, Manzar, Kumary, Burman, Spence, & Pandi-Perumal, 2018). It’s not just about feeling refreshed – quality sleep is key to our cognitive function, emotional well-being, and overall health (Medic, Wille, & Hemels, 2017).

Enter sleep apnea, the notorious thief of peaceful nights. It’s a condition where your breathing stops and starts repeatedly as you slumber. Think of it as a mischievous elf that blocks your airways every now and then (Benjafield et al., 2019).

But it’s not just about noisy snoring or feeling groggy the next day. Is linked with a host of not-so-fun health conditions. It’s like that one guy who never shows up to the party, bringing along his friends: heart disease, hypertension, diabetes, and depression (Lévy, Kohler, McNicholas, Barbé, McEvoy, & Somers, 2015).

And with this, we’ve just scratched the surface. Stick around as we dive deeper into this nighttime nuisance and the potential of supplements to help manage it.

Decoding Sleep Apnea

Picture sleep apnea as the invisible gremlin playing a discordant tune on your body’s orchestra. It’s a disorder punctuated by sudden halts and resumptions in breathing during sleep (Senaratna et al., 2017).

Symptoms? They can be sly – boisterous snoring, daytime fatigue, and awakening with a gasping or choking sensation. It’s easy to brush it off as just being a lousy sleeper. Sorry to burst the bubble, but it’s our little gremlin friend stirring up trouble (Peppard et al., 2013).

Wondering about the prevalence of this unwelcome guest? It’s more widespread than you’d expect. Nearly 1 billion people worldwide aged 30-69 years are estimated to have obstructive sleep apnea (Benjafield et al., 2019). What increases the risk? Factors include obesity, smoking, alcohol use, and even the genes passed down from your ancestors (Peppard et al., 2013).

Eager to show sleep apnea the exit? Stay tuned as we dig deeper into the details and explore how supplements may help you reclaim your night

The Importance of Sleep Quality

Let’s talk about sleep quality. It’s not just about getting your eight hours in; it’s about how well you snooze when the lights go out. Quality sleep is like a power-up for your body – it improves cognition, bolsters your immune system, and even helps keep your heart healthy (Irwin, 2019).

Now, let’s connect the dots with sleep apnea. Picture this: you’re in a peaceful slumber, dreaming about winning the lottery, when suddenly, you’re gasping for air. Not exactly a recipe for a good night’s sleep, is it?

This can severely disrupt REM sleep, which is a crucial phase of the sleep cycle, during which dreams occur and the brain processes memories (Rosenzweig et al., 2016).

During REM sleep sleep apnea episodes often intensify, leading to a severe drop in oxygen levels (Javaheri, 2017). This occurs due to the loss of muscle tone that characterizes this sleep stage. This can cause the airways to narrow or collapse more easily, exacerbating apnea symptoms (Joosten et al., 2014). 

Needless to say, turns your restful night into an obstacle course, leading to poor sleep quality and leaving you feeling more like a zombie than a refreshed, ready-to-take-on-the-day human being (Kendzerska et al., 2014), but I’m sure we don’t need to tell you that.

So, remember, quality sleep isn’t just a luxury—it’s a necessity. Your body will thank you for it!

Sleep Disordered Breathing (SDB): A Closer Look

It’s like a troublesome cousin to sleep apnea – they’re related, but with some key differences. SDB encompasses a range of breathing issues during sleep, of which sleep apnea is a notorious member (Senaratna et al., 2017).

It’s not just about the loud snoring (although, let’s be honest, that’s pretty disruptive too!). SDB can lead to low oxygen levels, fragmented sleep, and all-around bad vibes for your health. No surprise, when your body is unable to recover properly at night, whether that’s the brain function, heart, muscles, and more, you end up with cognitive impairments, high blood pressure, blood sugar abnormalities, and cardiovascular disease (Peppard et al., 2013).

Now, in case you want to start addressing this now, we’ve developed breathing exercises that promote easy nighttime breathing and put all of those resources for you in the Sleep Apnea Solution Book. The breathing routines have written instructions you can follow step-by-step or you can just press play and follow along the audio track to walk you through nighttime breathing exercises. Make it easy to boost natural breathing at night and take the first steps towards better sleep.

Delving Deeper: Obstructive Sleep Apnea (OSA)

OSA is the most common form of sleep apnea, where your throat muscles intermittently relax, blocking your airway (Senaratna et al., 2017). Faster breathing makes this more likely to happen by pulling the tongue into the airway like a suction effect, blocking off the airway like you can see below.

But don’t lose sleep over it (pun intended!). Understanding the problem is half the battle won. The other half? Well, that’s what the rest of this article is for!

Sleep Apnea Doesn’t Discriminate

While it’s a common belief that sleep apnea is a byproduct of being overweight because studies have shown that people with neck thickness and higher BMI have a greater risk (Peppard et al., 2000), it’s crucial to remember that sleep apnea is an equal opportunity annoyer. It doesn’t discriminate, folks! People of all ages, sizes, and neck circumferences can have sleep apnea (Lurie, 2011).

You may be surprised to know that even lean individuals and children can suffer from this condition (Kapur et al., 2002). So, remember, this is not just a ‘big guy’ problem. It’s a ‘big problem’ for guys (and gals) of all sizes!

A curious thought, isn’t it? It’s not just about a deviated septum, thick neck, or large waistline (Caples et al., 2005). Now, brace yourself for a real mind-bender. 

What’s Really Going on with Sleep Apnea

What if sleep apnea is actually a compensatory mechanism, a sort of a body’s DIY defense plan against further damage? Here’s the curveball – what if the body, in its wisdom, is trying to protect itself from the harm of… oxygen? 

Yep, oxygen, that life-giving stuff, can sometimes play the villain (Droge, 2002). In states of high inflammation, oxygen can morph into free radicals, causing damage (Kohen & Nyska, 2002). Imagine sleep apnea as the body’s attempt to shield its precious mitochondria (those little cellular powerhouses that use oxygen) from this harm.

Remember, the mitochondria produce melatonin and produce energy (also known as adenosine triphosphate or ATP). Energy is critical for endless functions in the body including but not limited to immune health and restful sleep.

Now, if this were true, our current strategies for researching sleep apnea are misguided and more research is needed. 

That would also mean our current approach to treatment, which is about getting more oxygen into the body, could be somewhat misguided as well. 

So, this is where it makes sense to consider additional options, like supplements, to address the underlying reasons for the body’s compensatory mechanisms (Kheirandish-Gozal & Gozal, 2014). 

Remember though, supplements are just the tip of the iceberg in what’s needed to address this issue. But hey, they’re worth mentioning, so let’s dive in, shall we?

Vitamins: Addressing the “Root Cause”

Now, let’s talk about vitamins. Imagine vitamins as a pack of multi-talented superheroes, each with a unique power, all dedicated to the mission of health. A number of these superheroes play a crucial role in sleep health (Grandner et al., 2010).

So, could pumping up your vitamin intake help poor sleep quality? 

Perhaps, in continuing this conversation we want to keep in mind,  the following questions:

1. Why are these vitamins low in the first place?
2. Are replacing these vitamins going to solve the underlying issue?
3. Are taking these vitamins supplement going to have the intended effect?

Let’s explore further!

Top Nutritional Supplements for Sleep Apnea

Alright, it’s time for the main event: the top nutritional supplements for sleep apnea.

Magnesium

First up, we have magnesium supplements, the body’s natural chill pill. This essential mineral is involved in over 300 enzymatic reactions in the body, including those that regulate sleep. Studies have shown that magnesium can help improve sleep efficiency and sleep time, especially in those with insomnia; on the flip side, a magnesium deficiency can result in insomnia and SDB, so topping up might just help out (Abbasi et al., 2012).

Adequate intake of magnesium is fun because there are so many factors that influence it being depleted and many different types that can be supplemented.

Types and Typical Dosages:

• Magnesium Citrate: Commonly used to support digestive health. Typical dosage: 200-400 mg per day.
• Magnesium Glycinate: Known for its calming effects and higher bioavailability. Typical dosage: 200-400 mg per day.
• Magnesium Oxide: Often used as a laxative or for heartburn relief. Typical dosage: 250-500 mg per day.
• Magnesium Threonate: Noted for its potential cognitive benefits. Typical dosage: 1,000-2,000 mg per day.
• Magnesium Malate: Sometimes used for muscle pain and fatigue. Typical dosage: 1,200-2,400 mg per day.

In what foods can you find this sleep-supporting superstar? Well, it’s present in a variety of foods. If you’re looking for vegetables, leafy greens like spinach and chard are a great source. You’ll also find magnesium in nuts and seeds, particularly pumpkin seeds. Whole grains and legumes, with black beans and quinoa being particularly high in magnesium. Even dark chocolate can give you a magnesium boost, in case you need another excuse to have a square or two (or three)!

Vitamin D

Next, we have vitamin D, which is actually a hormone! While vitamin D’s role in bone health, mood regulation, and how it supports immune health is best known, recent research has also suggested a link between vitamin D deficiencies and sleep disorders, including sleep apnea (McCarty et al., 2012).

One study found a significant correlation between low serum vitamin D levels and the severity of obstructive sleep apnea. The study suggested that vitamin D deficiency could contribute to the pathogenesis of sleep apnea, possibly by promoting inflammation and affecting the muscles that control our airways (Kerley et al., 2020). However, the connection isn’t entirely clear-cut, and more research is needed.

Types and Typical Dosages:

• Vitamin D2 (Ergocalciferol): Plant-based form. Typical dosage: 400-2,000 IU per day.
• Vitamin D3 (Cholecalciferol): Animal-based form, considered more effective. Typical dosage: 1,000-4,000 IU per day.

What I can tell you from my experience is that inflammation is sky high in people with sleep apnea. Vitamin D is a potent anti-inflammatory. However, I don’t love vitamin D in a supplement form. I much prefer natural sources such as the sun and some food sources of vitamin D such as fish skin, fish eye, egg yolks, and mushrooms.

Fish Oils

Let’s not forget omega-3 fatty acids. Yes, the stuff in fish oil. A study found that children with high blood levels of omega-3s had fewer sleep disturbances and a lower risk of sleep apnea (Montgomery et al., 2014). Omega-3 are prevalent and also known as fish oil supplements. Dietary sources of these beneficial fatty acids can, surprise, be obtained from fatty fish. 

Types and Typical Dosages:

• Eicosapentaenoic Acid (EPA): Typically found in fish oil. Typical dosage: 250-500 mg per day.
• Docosahexaenoic Acid (DHA): Also found in fish oil. Typical dosage: 250-500 mg per day.
• Alpha-linolenic Acid (ALA): Plant-based omega-3, found in flaxseeds, chia seeds, and walnuts. Typical dosage: 1,000-2,000 mg per day.

Tryptophan

Then there’s tryptophan, an amino acid that the body converts into the sleep hormone melatonin. Research suggests that tryptophan supplements can improve sleep and may be beneficial for sleep apnea (Hartmann, 1982). Tryptophan can be taken as a supplement, or it can be found in foods like turkey. There’s nothing like a nice post-Thanksgiving nap!

Types and Typical Dosages:

• L-Tryptophan: Commonly used form. Typical dosage: 500-1,000 mg per day.

Vitamin C

In the red corner, we have vitamin C, also known as ascorbic acid. It is perhaps most well known for how it supports immune health. Vitamin C is a stalwart champion in the health world and has been implicated in a study showing that it can mitigate some of the oxidative stress caused by sleep apnea (Lavie et al., 2009).

Types and Typical Dosages:

• Ascorbic Acid: Most common form. Typical dosage: 500-1,000 mg per day.
• Sodium Ascorbate: Buffered form, less acidic. Typical dosage: 1,000-2,000 mg per day.
• Calcium Ascorbate: Buffered form with added calcium. Typical dosage: 1,000-2,000 mg per day.

Don’t forget about the many food sources for vitamin C that include citrus fruits, bell peppers, strawberries, and broccoli. Who knew having healthy sleep could be so tasty? Now don’t forget herbal tea for sleep apnea. Some can contain vitamin C and have other benefits as well.

Vitamin E

In the blue corner, we have vitamin E. This is another powerful antioxidant that plays a crucial role in protecting the body’s cells from damage. Research suggests that vitamin E, along with vitamin C, may reduce blood pressure in patients with sleep apnea (Tan et al., 2013).

Types and Typical Dosages:

• Alpha-Tocopherol: Most common form. Typical dosage: 15-400 IU per day.
• Mixed Tocopherols: Includes alpha, beta, gamma, and delta forms. Typical dosage: 400-800 IU per day.
• Tocotrienols: Less common form with potentially higher antioxidant properties. Typical dosage: 50-200 mg per day.

But be careful! Antioxidant supplements like vitamin C and vitamin E can be double-edged swords. While vitamin E is an antioxidant and important for many body functions, it’s a bit like that friend who always insists on picking the karaoke song – great in the right doses but can cause some trouble if overdone. Think of free radicals as a bit like fire in a fireplace. When the fire is contained, it’s helpful and warming. When it’s out of control, it’s destructive. In a similar way, free radicals, while essential for cellular function and communication, can cause havoc when in excess (Lobo et al., 2010).

While vitamin E does combat free radicals, high doses of vitamin E supplementation have been associated with certain health risks, such as hemorrhagic stroke and even increased mortality (Bjelakovic et al., 2014). Vitamin E has also been linked to an increased risk of certain types of cancer, particularly prostate cancer in men (Klein et al., 2011). It’s like trying to put out a forest fire with a garden hose – it’s not addressing the root of the problem. Instead, we should aim to curb the uncontrolled production of free radicals, often due to high inflammation.

Remember, it’s not just about putting out the fire, it’s about preventing the spark in the first place. Remember this principle for vitamin E, vitamin C, and other antioxidants as well! Now that you know about some of the risks in supplementing vitamin E, it is safer to say that it is harder to go wrong with sources, including foods like almonds, spinach, and sweet potatoes.

If you want to learn how to make breathing easier naturally, get the Sleep Apnea Solution Book. It covers the top nutrition, environmental, circadian, and nervous system keys for sleep apnea. 

B Vitamins: Vitamin B1

First we’ll turn our attention to thiamine, also known as vitamin B1 (most commonly in the form of thiamine hydrochloride). Thiamine plays a crucial role in energy metabolism and the growth, development, and function of cells (Frank, 2019). 

Types and Typical Dosages:

• Thiamine Hydrochloride: Commonly used form. Typical dosage: 1.1-1.2 mg per day.
• Thiamine Mononitrate: Another common form. Typical dosage: 1.1-1.2 mg per day.
• Benfotiamine: Fat-soluble form with higher bioavailability. Typical dosage: 150-300 mg per day.

But, is there a connection between thiamine supplementation and sleep apnea? While there’s no other research suggesting thiamine supplementation can alleviate symptoms, studies show thiamine deficiency can cause a range of neurological issues, some of which can indirectly affect sleep quality (Frank, 2019).

However, it’s crucial to remember that more research is needed to fully understand the potential impact of thiamine on sleep apnea.

B Vitamins: Vitamin B6

You see, vitamins like B6 and B12 have been noted to directly or indirectly influence sleep quality. Vitamin B6, for example, is an essential player in the production of serotonin, a hormone that moonlights as a sleep regulator (Birdsall, 1998). 

Types and Typical Dosages:

• Pyridoxine Hydrochloride: Most common form. Typical dosage: 1.3-2.0 mg per day.
• Pyridoxal-5-Phosphate (P5P): Active form of vitamin B6. Typical dosage: 20-50 mg per day.

Dietary sources of vitamin B6 are similar to other b vitamins: chicken, turkey, beef, seafood, bananas, avocados, spinach, potatoes, legumes and whole grains.

B Vitamins: Vitamin B9

Next up on our list of b vitamins is folic acid, more commonly known as vitamin B9.

Folic acid is crucial for cell growth, metabolism, and the white and red blood cell formation in the bone marrow (Tamura & Picciano, 2006).

Types and Typical Dosages:

• Folic Acid: Synthetic form. Typical dosage: 400-800 mcg per day.

   

• 5-Methyltetrahydrofolate (5-MTHF): Active form of folate. Typical dosage: 400-800 mcg per day.

Now, theoretically more red blood cells would increase the oxygen carrying capacity in people apneic episodes, but more research is needed as many of the current studies focus on the broader B vitamins group, not specifically folic acid.

However, considering folic acid’s crucial role in overall health and wellbeing, it’s plausible that a deficiency could affect sleep patterns.

B Vitamins: Vitamin B12

Meanwhile, vitamin B12 has been linked to the regulation of the sleep hormone melatonin, your body’s natural Sandman (Okawa et al., 1997).

One study found that Vitamin B12 deficiency was more prevalent in patients with OSA (Gozal et al., 2013).

Types and Typical Dosages:

• Cyanocobalamin: Most common and stable form. Typical dosage: 2.4 mcg per day.

   

• Methylcobalamin: Active form, often used for neurological health. Typical dosage: 1,000-5,000 mcg per day.

   

• Adenosylcobalamin: Another active form, important for mitochondrial health. Typical dosage: 1,000-5,000 mcg per day.

It is Important to note that B vitamins are found in a healthy diet with a wide range of food sources, including whole grains, meat, egg yolks, legumes, seeds, and nuts. So a B complex vitamin is not the only option.

Melatonin

Ah, melatonin, the body’s in-house sandman, famous for its role in regulating our sleep-wake cycles and circadian rhythm. 

Yet research is limited regarding sleep apnea and melatonin. A study evaluated the efficacy and safety of prolonged-release melatonin in insomnia patients aged 55 years and older and showed improved sleep quality and alertness, but did not specifically focus on sleep apnea (Lemoine et al., 2007).

Types and Typical Dosages:

• Immediate-Release Melatonin: Helps with falling asleep. Typical dosage: 0.5-5 mg per day.

   

• Prolonged-Release Melatonin: Helps with staying asleep. Typical dosage: 2-10 mg per day.

However, it’s crucial to remember that while supplemental melatonin may have short term benefits for some people, taking this hormone as a supplement does not come without consequences.

While melatonin is generally considered safe for short-term use, it’s not without its potential downsides (Andersen et al., 2016). Side effects can include headache, dizziness, nausea, and drowsiness. There’s also the possibility of melatonin interacting with various medications including anticoagulants, immunosuppressants, diabetes medications and birth control pills (Auld et al., 2017).

Long-term use is less well-studied, and there’s some concern that extended melatonin use might suppress the body’s own production of the hormone, impacting the circadian rhythm (Srinivasan et al., 2011). Because melatonin is so important for the circadian clock, we’d recommend proceeding cautiously with supplemental forms.

Another reason to proceed with caution is that melatonin can relax the muscles in your airways too much leading to collapse. So, tread lightly!

Sleep Supplement Important Note

Remember, while supplements like vitamins and essential minerals can be beneficial, getting these nutrients from a balanced diet is usually the best way to go. Food sources provide a complex matrix of vitamins, minerals, fiber, and other substances that work together to promote good health.

Now, remember, supplements aren’t a magic bullet. They’re one part of the puzzle. A healthy lifestyle, including good sleep hygiene, is also crucial in having healthy sleep.

And of course, as with any supplementation plan, it’s always wise to discuss with your healthcare professional before starting a supplement. They can help you determine the correct dosage and monitor your progress, ensuring you get the most benefit while minimizing any potential risks.

Conclusion

In conclusion, managing sleep apnea effectively often involves a multifaceted approach that includes dietary and lifestyle changes, along with considering various supplements. We’ve explored the potential benefits of key supplements like magnesium, vitamin D, fish oils, tryptophan, vitamin C, vitamin E, and B vitamins, all of which play significant roles in supporting better sleep and overall health. Each of these nutrients can address specific aspects of sleep apnea, from reducing inflammation to regulating sleep-wake cycles and enhancing oxygen delivery.

Encouragingly, supplements can be a valuable addition to your sleep apnea management strategy. By ensuring your body receives the right nutrients, you can support your health and possibly reduce the severity of sleep apnea symptoms. However, it’s essential to approach supplementation thoughtfully and consult with healthcare professionals when making changes to your regimen.

Ready to take control of your sleep health? Check out our comprehensive book, which not only delves deeper into the best supplements for sleep apnea but also includes the most effective breathing routines. With accompanying audio tracks, you can start implementing these techniques tonight and work towards achieving the restful sleep you deserve. Don’t wait—start your journey to better sleep now!

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• Abbasi, B., Kimiagar, M., Sadeghniiat, K., Shirazi, M. M., Hedayati, M., & Rashidkhani, B. (2012). The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences, 17(12), 1161–1169. https://pubmed.ncbi.nlm.nih.gov/23853635/ 
• Kerley, C. P., Hutchinson, K., Bolger, K., McGowan, A., Faul, J., & Cormican, L. (2020). Serum vitamin D is significantly inversely associated with disease severity in Caucasian adults with obstructive sleep apnea syndrome. Sleep, 39(2), 293-300. https://pubmed.ncbi.nlm.nih.gov/26414899/ 
• Montgomery, P., Burton, J. R., Sewell, R. P., Spreckelsen, T. F., & Richardson, A. J. (2014). Fatty acids and sleep in UK children: subjective and pilot objective sleep results from the DOLAB study–a randomized controlled trial. Journal of Sleep Research, 23(4), 364–388. https://pubmed.ncbi.nlm.nih.gov/24605819/ 
• Hartmann, E. (1982). Effects of L-tryptophan on sleepiness and on sleep. Journal of Psychiatric Research, 17(2), 107-113. https://pubmed.ncbi.nlm.nih.gov/6764927/ 
• Lavie, L., Lavie, P. (2009). Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link. European Respiratory Journal, 33(6), 1467-1484. https://erj.ersjournals.com/content/33/6/1467 
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• Miller, E. R., Pastor-Barriuso, R., Dalal, D., Riemersma, R. A., Appel, L. J., & Guallar, E. (2005). Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Annals of internal medicine, 142(1), 37–46. https://pubmed.ncbi.nlm.nih.gov/15537682/ 
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If you’re like me, the idea of sifting through energy and metabolism supplement lists with 20+ energy supplements for chronic fatigue is more exhausting than the chronic fatigue you’re trying to fix. 

That’s why we’ve done the heavy lifting and curated the ultimate energy and metabolism supplement list with the top 10 best energy supplements for chronic fatigue that pack a powerful punch to fight fatigue. 

Say goodbye to energy and metabolism supplement information overload and hello to a chronic fatigue-free life! 

And, there are no affiliate links in this article… This is 100% unbiased non-profit-driven information so that you have an unbiased view of the best energy supplements to tackle chronic fatigue head-on.

(And, we’ll cover some supplement-free options as well!)

Let’s dive into this list of the best energy supplements for chronic fatigue!

1 Caffeine: The Classic Energy and Metabolism Supplement

First up is the classic stimulant to rule all (legal) energy supplements for chronic fatigue: caffeine.

Back in my day of chronic fatigue, I would consume about 2000-3000 milligrams of caffeine in various forms.

In fact, I could take a 200 mg tablet and fall asleep within 30 minutes.

Nonetheless, caffeine is one of the best energy supplements for a reason:

• Enhances alertness and focus
• Increases energy levels
• Diminishes perception of fatigue by up to 5.6% (Doherty & Smith, 2005)

However, the bigger the energy boost, the more careful you want to be about drawbacks:

• Dependency and tolerance: 50% of regular users experience withdrawal symptoms (Juliano & Griffiths, 2004)
• Sleep disturbances: consuming 400 mg within 6 hours of bedtime can reduce total sleep time by 1 hour (Drake et al., 2013). 

• Increased heart rate and blood pressure: high consumption is linked to a 22% higher risk of developing hypertension (Mesas et al., 2011)

Caffeine comes in many forms, such as caffeine anhydrous to a more “natural caffeine” like in coffee or in energy drinks.

In terms of a preferred brand, Elm & Rye caffeine supplements offer a convenient and controlled way to consume this energy supplement.

Elm & Rye Caffeine Supplements (and other caffeine supplements) also help you avoid all the sugary disasters that can accompany your energy drinks or coffee. 

Another brand is Natrol High Caffeine tablets.

As the name would suggest, Natrol High Caffeine tablets contain higher doses of caffeine. 

Natrol High Caffeine tablets will contain 200-400 mg whereas Elm & Rye Caffeine Supplements come in smaller doses.

Natural Stacks Smart Caffeine is another option. What sets Natural Stacks Smart Caffeine apart is that it contains other natural ingredients to help provide energy. So, consider Natural Stacks Smart Caffeine if you’re looking to decrease the number of pills you’re taking.

Now, I don’t want you to end up as I did, so here are some typical dosages

• Start low: 50-100 mg/day
• Moderate consumption: up to 400 mg/day (equivalent to 4 cups of coffee) (EFSA, 2015)

Now, think of caffeine as a last resort…

If caffeine is a “must” for you, then you may have bigger issues with chronic fatigue than you want to know about…

Caffeine does many nasty things to your body

• Dehydrates your cells
• Decreases mitochondrial function long term
• Keeps your nervous system in overdrive.

So please, from a former addict, natural caffeine is one of the most effective energy boosters… but it can quickly put you on a rollercoaster ride of an energy rush followed by energy crashes!

That’s why you should consider these other energy boosters…

2 “Adrenal Support” for Chronic Fatigue Syndrome

If you’re having cortisol and/or sleep issues with your chronic fatigue, then “adrenal support” can be one of the best energy supplements to deal with chronic fatigue symptoms.

Quite a few “blends” contain a potpourri of compounds that can help normalize your stress hormones while boosting energy levels.

Here are three popular brands of this energy supplement in order of increasing strength

Adrenal Edge Liquid Drops

• Adrenal Edge Liquid Drops feature a blend of natural adaptogenic herbs, including ashwagandha, Rhodiola, and holy basil, which help the body adapt to stress for sustained energy
• Adrenal edge liquid drops thus allow for easy dosage adjustments and quick absorption

NutraTemple Adrenal Support

• NutraTemple Adrenal Support contains natural ingredients like vitamin C, vitamin B6, and magnesium that are essential for adrenal gland function, hormone production, and sustained energy
• NutraTemple Adrenal Support contains adaptogenic herbs, such as ashwagandha and Rhodiola, to help combat stress and fatigue

EU Natural Vitality Capsules

• EU Natural Vitality Capsules are formulated with essential vitamins, minerals, and plant-based ingredients like Vitamin B Complex, Vitamin C, Vitamin D, Magnesium, and Ashwagandha,
• EU Natural Vitality Capsules promote energy, immune function, and stress management. 

Pure Encapsulation Adrenal Capsules

• Contains actual adrenal gland extracts which makes it different than other energy supplements for chronic fatigue
• Provides essential nutrients and bioactive compounds to support adrenal hormone production and stress response
• Free from artificial additives and common allergens, making it suitable for individuals with dietary sensitivities

Now, there is no scientific research on these energy supplements for chronic fatigue, but that doesn’t mean they’re “useless.”

Many people report positive effects, but, if they’re anything like our clients, they go through a honeymoon period of “This is fantastic for about 3-4 weeks” before they feel like it stops working (more on that later).

And, lastly, adrenal gland extracts are fairly strong. 

That is, they will reduce symptoms in most people… but will create a strong dependency and, ultimately, make fatigue symptoms worse.

3 B-Vitamins: Energy Boost Nutrients

When your B vitamins are low… so are your energy levels (Kennedy, 2016) which is why they’re on this list of the best energy supplements to combat chronic fatigue.

Here are the three main B vitamins that can provide a sustained energy boost for persistent fatigue:

1. Vitamin B6 (Pyridoxine): Involved in over 100 enzyme reactions in the body, vitamin B6 is essential for cellular energy production, neurotransmitter synthesis, and immune function (Hvas & Juul, 2004). The recommended daily dosage for adults ranges from 1.3 to 1.7 mg per day, depending on age and gender (Institute of Medicine, 1998).
2. Vitamin B9 (Folic Acid): Folic acid, also known as folate, plays a critical role in cell division, DNA synthesis, and the production of red blood cells. It also helps convert homocysteine, an amino acid, into methionine, thereby reducing the risk of cardiovascular disease (Brouwer et al., 1999). The recommended daily dosage for adults is 400 mcg per day (Institute of Medicine, 1998).
3. Vitamin B12 (Cobalamin): Vitamin B12 is necessary for red blood cell formation, energy production, and neurological function. It also helps maintain the health of nerve cells and supports the synthesis of DNA (Langan & Goodbred, 2017). The recommended daily dosage for adults is 2.4 mcg per day (Institute of Medicine, 1998).

And, the dosages above are typically much lower than how most people supplement for chronic fatigue… find what works for you!

Now, I typically recommend taking a B-complex as an energy supplement… but I always prefer our clients to get B vitamins from natural food sources for a natural energy boost.

Also… you must recognize that B vitamins are deficient in the first place because your mitochondria can’t burn fat so they use up B vitamins in carbohydrate metabolism (which is an unsustainable biochemical dependency).

That is, you get more energy NOT from B vitamins per se… 

You get more energy from properly functioning mitochondria

4 Coenzyme Q10: A Cellular Powerhouse

Coenzyme Q10 (CoQ10) joins the energy supplement list as it plays a critical role to increase energy production in the mitochondria, where it helps generate ATP (adenosine triphosphate; (Crane, 2001). 

Since chronic fatigue is recognized as a mitochondria issue by many, CoQ10 has become more of a popular choice.

Here are the benefits of CoQ10:

• Supplementing with CoQ10 may help alleviate fatigue and improve overall energy levels, especially in individuals with low CoQ10 levels such as those with chronic fatigue (Cordero et al., 2012).
• Studies have suggested that CoQ10 may improve cognitive function and memory, which can be beneficial for individuals suffering from chronic fatigue (Young et al., 2007).
• CoQ10 is known for its cardioprotective properties, as it may help maintain heart health by improving endothelial function and reducing oxidative stress (Rosenfeldt et al., 2003).

Typical dosages range from 100-300 mg per day.

Despite our work with our clients being “mitochondria focused,” we rarely use CoQ10.

Why’s that? 

In the grand scheme of healing your mitochondria, CoQ10 is worth a decent 5% toward your energy metabolism.

That’s why many people who take CoQ10 don’t really feel any effects in comparison to the other energy boosters on this list… but, make no mistake, it will help provide a natural energy boost.

5 L-Carnitine: Fueling Energy and Metabolism

L-Carnitine is an amino acid derivative that transports long-chain fatty acids into the mitochondria, where they are oxidized to generate ATP (adenosine triphosphate), the body’s primary source of energy (Stephens et al., 2007).

Here’s how L-carnitine can help with chronic fatigue:

• Enhanced energy levels: L-carnitine supplementation has been shown to boost energy levels in individuals with chronic fatigue by improving fatty acid oxidation and ATP production. A daily dosage of 1,000 to 3,000 mg is commonly recommended for adults experiencing fatigue or low energy levels (Plioplys & Plioplys, 1997).
• Improved endurance and exercise performance: L-carnitine has been linked to increased endurance and enhanced exercise performance due to its role in fatty acid metabolism. Studies have suggested that a daily dosage of 2,000 to 4,000 mg may help improve physical performance and reduce fatigue during exercise (Rebouche, 2004).
• Support for brain function: L-carnitine may also contribute to better brain function by protecting neurons from oxidative stress and promoting the synthesis of essential neurotransmitters. Although there is no specific dosage established for cognitive benefits, a daily dosage of 1,000 to 3,000 mg is generally suggested based on its overall positive effects on health and energy levels (Smeland et al., 2012).

Many may not benefit from L-carnitine because no matter how many fatty acids you can transport into your mitochondria, sometimes they simply can’t burn fat. 

In fact, for most people with chronic fatigue, their body’s ability to burn fat is poor… so keep that in mind!

6 D-Ribose: Replenishing Energy Stores

D-Ribose helps ATP production (Hellsten et al., 2004) which is why it joins this list of the best energy supplements for chronic fatigue. 

Let’s see what D-ribose can do:

• Improved energy levels: D-ribose supplementation has been shown to increase cellular energy levels in individuals with chronic fatigue by enhancing ATP production. A daily dosage of 5 to 15 grams, divided into two or three doses, is commonly recommended for adults experiencing fatigue or low energy levels (Teitelbaum et al., 2006).
• Faster recovery from exercise: D-ribose may help improve post-exercise recovery by replenishing depleted ATP stores in muscles more quickly. A daily dosage of 5 to 10 grams, taken before and/or after exercise, has been suggested to support faster recovery and reduce exercise-induced fatigue (Hellsten et al., 2004).
• Support for heart health: D-ribose has been found to support heart health by promoting ATP synthesis and improving myocardial energy metabolism. A daily dosage of 5 to 15 grams, divided into two or three doses, has been recommended for individuals with cardiovascular concerns, though it is essential to consult with a healthcare professional before starting supplementation (Omran et al., 2003).

WARNING: If you have blood sugar issues, D-Ribose can worsen them!

7 Ginseng: A Traditional Energy Tonic

Ginseng, a renowned natural solution to combat fatigue and improve energy levels as a natural energy supplement (Kim, 2018).

And, yes, ginseng is also included in many energy drinks for a much-needed energy boost.

Benefits for Chronic Fatigue: 

A study with 90 participants found that ginseng extract significantly reduced fatigue in chronic fatigue syndrome patients, with a 20% reduction in fatigue severity (Kim et al., 2013).

Enhanced Energy Levels: 

A systematic review and meta-analysis of 12 randomized controlled trials showed that ginseng supplementation reduced fatigue and increased energy levels in healthy individuals (Leung & Wong, 2019).

Improved Cognitive Function:

A double-blind, placebo-controlled study with 30 participants demonstrated that a single dose of ginseng (200/400 mg) improved memory, attention, and processing speed by 7.5% (Reay et al., 2010).

A 12-week study with 58 Alzheimer’s patients revealed that ginseng supplementation (4.5 g/day) improved cognitive performance by 8.4% (Lee et al., 2018).

Support for Immune Health: 

A double-blind, placebo-controlled study with 227 participants found that ginseng administration (100 mg/day) for 12 weeks increased the production of immune cells, enhancing resistance to infections (Scaglione et al., 1996).

However, ginseng can create the same issues as caffeine (at much lower levels).

When your metabolic engines (your mitochondria) are broken down…

Adding in “boosters” (like ginseng and caffeine) can lead to further damage.

8 Maca: An Ancient Superfood for Energy and Vitality

Maca (Lepidium meyenii) is a nutrient-rich root vegetable that has been traditionally used in South America as a natural energy supplement.

Benefits for Chronic Fatigue: Maca may alleviate symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and improving mitochondrial function (Vecera et al., 2007; Zhang et al., 2019).

Enhanced Energy Levels: A systematic review of 4 randomized controlled trials found maca supplementation increased subjective energy levels in healthy individuals (Shin et al., 2010).

Improved Endurance and Physical Performance: A 14-day study with 8 male cyclists showed that maca extract (1.5 g/day) improved time trial performance by 1.28% compared to placebo (Stone et al., 2009).

Support for Hormone Balance: Maca has been found to modulate hormone levels, potentially benefiting menopausal women by alleviating symptoms like hot flashes and mood swings (Brooks et al., 2008; Meissner et al., 2006).

9 Magnesium: A Key Mineral for Energy and Relaxation

Magnesium is an essential mineral that plays a crucial role in energy production, muscle and nerve function, and promoting relaxation and sleep quality.

As a result, Magnesium is one of the most versatile and best energy supplements for chronic fatigue.

Benefits for Chronic Fatigue: 

• Magnesium deficiency has been linked to chronic fatigue syndrome, and supplementation may help alleviate symptoms by improving energy production at the cellular level (Cox et al., 1991).

Improved Energy Levels:

• Magnesium is a vital cofactor in ATP production, the primary energy source for cells, and adequate levels contribute to overall energy and vitality (Volpe, 2013).

Enhanced Muscle and Nerve Function

• Magnesium supports muscle and nerve function by regulating calcium levels, which are essential for proper muscle contraction and nerve signal transmission (de Baaij et al., 2015).

Support for Sleep Quality

• Magnesium has a calming effect on the nervous system and has been shown to improve sleep quality by promoting relaxation and reducing nighttime awakenings (Abbasi et al., 2012).

Types and Dosages of Magnesium

• Common types of magnesium supplements include magnesium oxide, magnesium citrate, magnesium glycinate, and magnesium malate.
• The Recommended Dietary Allowance (RDA) for magnesium is 310-420 mg daily for adults, depending on age and sex (Institute of Medicine, 1997).

Honorable Mentions before we get to number 10!

I want to briefly mention a few items that almost made the list… but didn’t for various reasons.

Energy Multivitamin

An energy multivitamin can be a very attractive idea.

An energy multivitamin can contain many of the above compounds and energy-boosting nutrients.

So, as an energy booster, it would seem like a great idea to just pack everything into a single energy multivitamin, right?

Wrong.

Why?

Most multivitamins pack a bunch of different ingredients… but fail to provide a high enough of the specific ingredient that might be the best for you.

Think of multivitamins as a “jack of all trades, but master of none”

Prohealth energy NADH

ProHealth Energy NADH is a dietary supplement designed to support energy production and mental clarity. 

However, for ProHealth Energy NADH and other NADH supplements… I don’t love them.

Yes, they will temporarily boost energy and mental clarity… but not in the long term.

Your body makes its own NADH and it’s involved in your mitochondria and circadian rhythms.

When you ingest NADH externally, then this causes some issues with your body’s own natural ability to properly produce and regulate NADH. 

Hence, I don’t love NADH products.

Iron Supplement

Oftentimes people are low on iron… hence an iron supplement can help.

However, many times this deficiency is driven by inflammation or poorly functioning mitochondria that aren’t using iron properly.

Brief detour complete!

Let’s get to the finale with number 10!

10 Mitochondrial Support

We’ve done it! We’ve made it to number 10 of the best energy supplements for chronic fatigue.

But first… let me ask…

Are you really going to take all 9 of the above energy supplements or try them out over the course of months?

That’s why I don’t love these lists of energy supplements for chronic fatigue.

Yes, you may be very driven to get your energy levels back.

But assuming that any one of these energy supplements is going to be the “holy grail” of your recovery is just as dangerous as overdosing on some of the above energy supplements.

If you’ve noticed, a lot of these supplements center around your mitochondria function.

So, why not just use some direct mitochondria supplements?

Plenty of these types of supplements contain ATP, PQQ, and other such mitochondria-specific chemicals.

But, here’s the thing…

They may give you a temporary, much-needed energy boost…

The real question isn’t “What are the best energy supplements for chronic fatigue?”

What you need to be asking is “Why are my energy levels so low in the first place?”

Your Mitochondria are the Ultimate Energy Booster

As we’ve been mentioning throughout this article, nearly all aspects of energy metabolism rely on your mitochondria.

When those aren’t working right, that’s when you’re out here going through lists of supplements hoping “This is the one!”

In reality, none of them will help your mitochondria fully repair.

That’s why we’ve made our short “primer” on mitochondria on how they related to your specific conditions here: https://optimalcircadianhealth.com/learn/

Enjoy!

Here’s to fewer supplements and more life!

Sincerely,

Dylan Petkus, MD

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• Stone M, Ibarra A, Roller M, Zangara A, Stevenson E. A pilot investigation into the effect of maca supplementation on physical activity and sexual desire in sportsmen. J Ethnopharmacol. 2009;126(3):574-576. Link
• Brooks NA, Wilcox G, Walker KZ, Ashton JF, Cox MB, Stojanovska L. Beneficial effects of Lepidium meyenii (Maca) on psychological symptoms and measures of sexual dysfunction in postmenopausal women are not related to estrogen or androgen content. Menopause. 2008;15(6):1157-1162. Link
• Meissner HO, Kapczyński W, Mscisz A, Lutomski J. Use of Gelatinized Maca (Lepidium peruvianum) in Early Postmenopausal Women. Int J Biomed Sci. 2006;2(2):143-159. Link
• Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet. 1991;337(8744):757-760. Link
• Volpe SL. Magnesium in disease prevention and overall health. Adv Nutr. 2013;4(3):378S-383S. Link
• de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol Rev. 2015;95(1):1-46. Link
• Abbasi B, Kimiagar M, Sadeghniiat K, Shirazi MM, Hedayati M, Rashidkhani B. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. J Res Med Sci. 2012;17(12):1161-1169. Link
• Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington (DC): National Academies Press (US); 1997. Link

Glutathione, often dubbed the “master antioxidant,” plays a crucial role in maintaining our overall health and well-being. 

But, how do you know which one is the most effective? 

In this article, we’ll dive into the world of S-Acetyl L Glutathione and liposomal glutathione, comparing their properties, benefits, and bioavailability. 

 Major questions answered in this article:

• What is S-Acetyl L Glutathione, and what are its health benefits?
• What is liposomal glutathione, and how does it promote well-being?
• How do S-Acetyl L Glutathione and liposomal glutathione compare in terms of bioavailability and absorption?
• What factors should you consider when choosing between these two supplement forms?
• What does recent research say about the efficacy of S-Acetyl L Glutathione and liposomal glutathione?

And, of course, “Do you even need supplemental glutathione?”

Let’s dive in!

Glutathione Supplements Overview

Glutathione, a small yet mighty molecule, has taken the spotlight in the health and wellness world. 

Note, when we’re referring to “glutathione” this is technically “reduced glutathione”

Reduced glutathione is the basic form that is actually active in your body.

With its superhero-like abilities to fight off nasty villains in our bodies, it’s no wonder that it has been dubbed the “master antioxidant.”

Definition and Importance

Reduced glutathione is a tripeptide composed of three amino acids: cysteine, glutamic acid, and glycine (Wu et al., 2004). 

The glutathione molecule plays a crucial role in maintaining our bodies’ finely tuned balance, acting as a cellular guardian to protect us from the constant onslaught of oxidative stress and toxic compounds (Sies, 1999).

Produced naturally in our cells, glutathione is essential for numerous cellular processes, such as DNA synthesis and repair, protein synthesis, and enzyme activation (Lu, 2013).

The Master Antioxidant?

But it doesn’t stop there; this multitasking molecule also participates in immune system regulation and the recycling of other antioxidants, like vitamins C and E (Forman et al., 2009). 

In fact, reduced glutathione is up to 5,000 times more effective than other antioxidants, such as vitamin C, at quenching free radicals (Pizzorno, 2014).

However, don’t be fooled by the trendiness of “master antioxidant” because this is not as simple as it seems…

Role as an Antioxidant and Detoxifying Agent

As a powerful antioxidant, glutathione wields its formidable powers to neutralize reactive oxygen species (ROS), those pesky free radicals that can cause damage to our cells and contribute to aging and various diseases (Rahman, 2007). 

By keeping ROS in check, glutathione helps to maintain the delicate balance between oxidation and antioxidation, ensuring that our cells stay healthy and vibrant (Sies, 2015).

In addition to its antioxidant prowess, glutathione is also an expert in the art of detoxification. Our bodies are constantly exposed to a barrage of toxins, both from our environment and as a byproduct of normal metabolic processes (Liska, 1998). 

Glutathione inside cells jumps into action, binding to these toxins and transforming them into less harmful compounds that can be safely eliminated (Ballatori et al., 2009). By acting as the body’s natural detoxifier, glutathione plays a vital role in maintaining our health and well-being.

Here’s some more specifics on where glutathione functions in your body

Immune system Health

Glutathione enhances immune cell function by promoting the appropriate proliferation, activation, and differentiation of immune cells, such as lymphocytes and macrophages (Dröge & Breitkreutz, 2000).

It modulates inflammation by regulating the production of pro-inflammatory and anti-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) (Dröge & Breitkreutz, 2000).

Chronic diseases often have immune dysfunction. So, chronic disease management may benefit from glutathione use.

Liver detoxification

Glutathione supports healthy liver function and detoxification by neutralizing toxins, such as heavy metals (e.g., mercury, cadmium), drugs (e.g., acetaminophen), and environmental pollutants (e.g., polycyclic aromatic hydrocarbons) (Lu, 2013).

It also enhances the activity of detoxification enzymes, such as glutathione S-transferases (GSTs), which conjugate toxins to Glutathione, facilitating their elimination (Lu, 2013). Altogether, this would boost liver health.

Anti-aging effects

Healthy young people have been found to have higher glutathione levels than unhealthy elderly counterparts.

Glutathione offers anti-aging benefits and promotes healthy aging due to its potent antioxidant capacity, which protects cells from damage caused by oxidative stress and inflammation (Weschawalit et al., 2017).

• Brain Health

  In particular, glutathione has been shown to support neuron health. In fact, some practitioners use it for those with Alzheimer’s disease as glutathione treats cognitive problems.

  It prevents the formation of advanced glycation end products (AGEs), which contribute to age-related diseases, such as diabetes, cardiovascular disease, and neurodegenerative disorders (Nagai et al., 2012).

  Glutathione supports skin health by inhibiting melanogenesis, reducing age spots, and improving overall skin tone (Weschawalit et al., 2017).

  That’s why people are so attracted to the idea of supplementing with glutathione (I’ll rip on that in a bit).

  However, you need to consider the different forms of glutathione to know which one is best for you.

Introduction to S-Acetyl Glutathione and liposomal glutathione

Even the most powerful heroes sometimes need a boost, and Glutathione is no exception. 

While our valiant tripeptide is crucial for maintaining cellular health, its Achilles’ heel lies in its limited bioavailability. 

In other words, orally ingested Glutathione struggles to reach the cells where it’s needed most, leaving them vulnerable to the nefarious effects of oxidative stress (Weschawalit et al., 2017). 

Enter S-Acetyl L Glutathione and Liposomal Glutathione – two innovative forms of our beloved antioxidant designed to overcome reduced glutathione’s bioavailability woes. With their unique properties, these dynamic derivatives swoop in to save the day, ensuring that Glutathione can reach its cellular targets and fulfill its destiny as the master antioxidant.

Lifestyle Changes and Home Remedies for Sleep Apnea

Development of alternative forms.

Acetyl Glutathione: The Stealthy Sidekick

In the quest for enhanced bioavailability, scientists have turned to S-Acetyl L Glutathione, an acetylated form of Glutathione that has a stylish acetyl group on a sulfur atom acting like a superhero’s cape (Richman & Meister, 1975). 

Acetylated glutathione not only increases the stability and lipophilicity of Glutathione but also allows it to sneak past the cellular defenses and enter cells more efficiently (Cacciatore et al., 2010). 

Once inside, the acetyl group is removed, and the non-acetylated form of Glutathione springs into action, ready to neutralize harmful free radicals and detoxify rogue toxins.

Liposomal Glutathione: The Mighty Micronaut

The second member of our dynamic duo, Liposomal Glutathione, takes a different approach to tackle the bioavailability conundrum. 

Instead of using an acetylated glutathione structure, this form encases it within a minuscule, spherical structure called a liposome (Kidd, 2011). 

This liposome allows oral ingestion to be an effective avenue of administration.

These lipid-based vehicles not only protect Glutathione from degradation but also facilitate its passage across cell membranes (Viscovich et al., 2004). 

Once delivered to its destination, Glutathione disembarks from its liposomal vessel and gets down to the business of combating oxidative stress.

Now, let’s compare

In-Depth Comparison of S-Acetyl L Glutathione and Liposomal Glutathione

Let’s compare stability, uptake, price, and individual needs that would help you consider which one dietary supplement may be best for you.

Stability

• As the acetyl group protects glutathione, it is more stable in the gastrointestinal tract (Wu et al., 2004). This increased stability keeps the glutathione molecule intact as it is absorbed and used by the body.
• Liposomal Glutathione relies on liposomal encapsulation technology to enhance stability in the gastrointestinal tract. The liposomal encapsulation shields glutathione from degradation and improves its bioavailability (Kidd, 2011). However, it may not be as stable as S-Acetyl L Glutathione.

Cellular Uptake

• While both S-Acetyl L Glutathione and Liposomal Glutathione display improved cellular uptake compared to regular glutathione, the specific degree of improvement between the two forms has not been well established in the literature.
• S-Acetyl L Glutathione, which facilitates transport across cell membranes for efficient cellular uptake including the blood-brain barrier (Wu et al., 2004).
• Liposomal Glutathione is encapsulated within liposomes, which merge with cell membranes and release glutathione into the cells (Akbarzadeh et al., 2013). The degree to which liposomal encapsulation improves cellular uptake relative to S-Acetyl L Glutathione is not known, but it is likely it crosses the blood-brain barrier more efficiently.

Price Comparison

Several oral glutathione supplements exist… I don’t have a preferred brand, this is just an overview

• Prices for S-Acetyl L Glutathione and Liposomal Glutathione supplements can vary widely depending on the brand, quality, and quantity. On average, S-Acetyl L Glutathione supplements may range from $30 to $50 for a month’s supply, while Liposomal Glutathione supplements can range from $50 to $80 for a month’s supply.
• The higher price of Liposomal Glutathione is due to the complexity and cost associated with liposomal encapsulation technology.

Overall, S-acetyl L glutathione wins the price comparison which is important because, quite simply, you could just ingest more S-acetyl L glutathione to overcome any of the benefits of its liposomal counterpart.

Individual Needs and Preferences

• The choice between S-Acetyl L Glutathione and Liposomal Glutathione may depend on individual needs and preferences. Some factors to consider include:
1. Tolerability: Some individuals may find one form of glutathione more tolerable than the other due to differences in formulation, taste, or potential side effects.
2. Specific Health Conditions: Certain health conditions, such as chronic liver disease, neurodegenerative disorders, or autoimmune diseases, may influence the choice of glutathione form.
• Liver issues do better with liposomal
• Autoimmune issues do better with liposomal and n-acetyl cysteine (NAC)
• Neurodegeneration does better with acetyl glutathione 
3. Budget: As Liposomal Glutathione is generally more expensive than S-Acetyl L Glutathione, budget constraints may play a role in the decision-making process.
4. Convenience: Some individuals may prefer acetyl glutathione vs liposomal due to ease of administration or dosage requirements.

Ultimately, the choice between S-Acetyl L Glutathione and Liposomal Glutathione should be made in consultation with a healthcare professional, taking into consideration individual needs, health conditions, and preferences.

Now, all that is glutathione doesn’t glitter.

I’ve been in your shoes grabbing for supplements, chemicals, and peptides trying to get my health back to 100%.

It’s a desperate scramble that brings us to articles like this, where we want some reassurance about a new silver bullet.

But, here’s the brutal truth.

Glutathione may help a bit, but it’s yet another band-aid.

That’s why the question is NOT “Should I go with acetyl glutathione or liposomal?”

You need to ask yourself “Why is my glutathione low in the first place?”

Why your Glutathione is Low

There are two main reasons.

First, you have rampant inflammation throughout your body that is depleting you of glutathione.

This inflammation is very likely due to environmental issues and a poor circadian rhythm (those are typically what we see in our clients).

For instance, healthy liver function requires a solid circadian rhythm. When your liver health isn’t great, it will use more glutathione and deplete you!

Another example is the dysregulation of your immune system health.

When your circadian rhythm is off, inflammation will go higher, and this triggers your immune system.

Then, yet again, you deplete yourself of glutathione.

Mitochondria and Glutathione

The other component is that poorly functioning mitochondria lead to a more free radical generation that leads to more inflammation.

And, poorly functioning mitochondria tie into the second cause of you needing glutathione…

The second big piece is that you have a reduced capacity to make your own glutathione 

And guess what helps you make glutathione?

Your mitochondria (Lu, 2013).

Healthy mitochondria in a healthy human body produce the glutathione levels you need to thrive.

So, if you don’t reverse those two issues above, then your body begins to make less glutathione by itself and that leads to you being dependent on a supplement for an essential human function.

How to Naturally Boost Your Glutathione

So, the question isn’t “Which glutathione” is best… 

The real question is “What do you need to know about your mitochondria?”

That’s why we made our masterclass that breaks these concepts down.

You can access it for free here: https://optimalcircadianhealth.com/class

Enjoy! Your health and glutathione levels will thank you!

Best,

Dylan Petkus, MD

References:

• Wu, G., Fang, Y. Z., Yang, S., Lupton, J. R., & Turner, N. D. (2004). Glutathione metabolism and its implications for health. The Journal of Nutrition, 134(3), 489-492.
• Sies, H. (1999). Glutathione and its role in cellular functions. Free Radical Biology & Medicine, 27(9-10), 916-921.
• Lu, S. C. (2013). Glutathione synthesis. Biochimica et Biophysica Acta (BBA) – General Subjects, 1830(5), 3143-3153.
• Forman, H. J., Zhang, H., & Rinna, A. (2009). Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine, 30(1-2), 1-12.
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684512/
• Sies, H. (2015). Oxidative stress: a concept in redox biology and medicine. Redox Biology, 4, 180-183.
• Liska, D. J. (1998). The detoxification enzyme systems. Alternative Medicine Review, 3(3), 187-198.
• Ballatori, N., Krance, S. M., Notenboom, S., Shi, S., Tieu, K., & Hammond, C. L. (2009). Glutathione dysregulation and the etiology and progression of human diseases. Biological Chemistry, 390(3), 191-214.
• Weschawalit, S., Thongthip, S., Phutrakool, P., & Asawanonda, P. (2017). Glutathione and its antiaging and antimelanogenic effects. Clinical, Cosmetic and Investigational Dermatology, 10, 147-153.
• Richman, P. G., & Meister, A. (1975). Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. Journal of Biological Chemistry, 250(4), 1422-1426.
• Cacciatore, I., Cornacchia, C., Pinnen, F., Mollica, A., & Di Stefano, A. (2010). Prodrug approach for increasing cellular glutathione levels. Molecules, 15(3), 1242-1264.
• Kidd, P. M. (2011). Glutathione: systemic protectant against oxidative and free radical damage. Alternative Medicine Review, 1(3), 155-176.
• Viscovich, M., Lykkesfeldt, J., & Poulsen, H. E. (2004). Vitamin C pharmacokinetics of plain and slow release formulations in smokers. Clinical Nutrition, 23(5), 1043-1050.
• Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013 May;1830(5):3143-53. doi: 10.1016/j.bbagen.2012.09.008. Epub 2012 Sep 17. PMID: 22995213; PMCID: PMC3549305.
• Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S. W., Zarghami, N., Hanifehpour, Y., … & Nejati-Koshki, K. (2013). Liposome: classification, preparation, and applications. Nanoscale Research Letters, 8(1), 102.

Welcome, dear reader, to the curious world of delta sleep-inducing peptide (DSIP)! 

You may have the same thought I had when a client mentioned this to me… 

“What on earth is that?” and, “Is it a secret sleep potion?” 

Well, buckle up, because we’re about to dive deep into this fascinating molecule.

Here’s what we’ll uncover in this wild rollercoaster of an article:

• What is Delta sleep inducing peptide, and how was it discovered?
• How does Delta sleep inducing peptide work its magic in your brain?
• What effects does Delta sleep inducing peptide have on sleep, stress, and your trusty neurons?
• Can Delta sleep inducing peptide help chronic insomniac patients and those with other sleep disorders? (And even neurodegenerative diseases?) 
• What does the current research and clinical trials say about Delta sleep inducing peptide?
• Are there any side effects, and is Delta sleep inducing peptide safe to use?
• How can you get your hands on some Delta sleep inducing peptide, and what’s the right dosage?
• What to consider instead of injecting yourself with “internet peptides”

We promise to keep things light, fun, and easy to understand – because let’s face it, science can be a snooze-fest sometimes.

So, without further ado, let’s embark on a journey through the enchanting realm of delta sleep-inducing peptide, starting with its background and discovery.

Background and Discovery

Once upon a time in the groovy 1970s, a group of curious scientists was on a mission to unravel the mysteries of the brain. They serendipitously stumbled upon a fascinating discovery: a tiny peptide that had the power to lull our minds into a blissful slumber. 

This molecular marvel, first identified and isolated from rabbit brain cerebral venous blood, was christened “Delta Sleep-Inducing Peptide,” or DSIP for short (Monnier et al., 1977).

(In fact, when they found it, they thought it was a new unknown hypothalamic hormone)

What is DSIP: definition and biochemical properties

Delta sleep inducing peptide is a naturally occurring substance and neuropeptide family – a group of small proteins that act as brain messengers. It’s like a molecular lullaby that’s made up of a simple yet harmonious sequence of just nine amino acids. 

Despite its small size, Delta sleep inducing peptide has some remarkable biochemical properties. 

For instance, it’s highly resistant to degradation by enzymes, which allows it to stick around and work its magic for longer. 

It’s also relatively stable at room temperature, which is a bonus for those who need to store it for future use (or impromptu nap sessions).

Delta sleep inducing peptide also crosses the blood brain barrier like it has a VIP pass.

Sources and production of DSIP

Delta sleep inducing peptide is primarily synthesized and released in our brains, where it orchestrates its sleep-inducing symphony. However, just like a true multitasker, Delta sleep inducing peptide can also be found in other organs of the body, such as the heart, kidneys, and liver. This suggests that it might have other roles beyond regulating our sleep cycles.

While we’ve learned a great deal about Delta sleep inducing peptide since its discovery, there are still many unanswered questions regarding its production and distribution throughout the body. 

It’s found in pretty much every organ system you can name which is odd for a “sleep” peptide… Don’t ya think? (we’ll dive into this later)

Sleep Promoting Substance – Mechanism of Action

Once upon a time in the land of neurons, Delta sleep inducing peptide embarked on an adventure through the central nervous system (CNS). DSIP promotes sleep by interacting with various brain regions that govern sleep, such as the hypothalamus and the brainstem (Kastin & Akerstrom, 2003). 

Delta sleep inducing peptide’s magical touch influences the release of certain neurotransmitters, like GABA, which helps calm the excited chatter of neurons and ushers in peaceful slumber (Siva Sankar & Swathi, 2013).

Impact on sleep regulation and sleep stages

Delta sleep inducing peptide’s sleep-inducing prowess lies in its ability to gently sway the delicate balance of our sleep-wake cycle. 

The sleep onset mechanism is a little complicated…

Human plasma DSIP decreases at the beginning of sleep (but giving someone Delta sleep inducing peptide induces sleep) (Schoenenberger et al., 1988). 

The reason for this is that Delta sleep inducing peptide goes up… and then down.

This physiological “up and down” sends the signal to promote sleep.

This pattern of Delta sleep inducing peptide is particularly influential during slow-wave sleep (SWS) and rapid eye movement (REM) sleep, the phases when we dream and rejuvenate our minds (Kastin & Akerstrom, 2003).

Role in stress response modulation

Delta sleep inducing peptide’s talents extend beyond the realm of sleep. 

Our versatile peptide also moonlights as a stress-buster, helping to quell the cacophony of cortisol and other stress hormones (Siva Sankar & Swathi, 2013). By taming the tempest of our body’s stress response, Delta sleep inducing peptide promotes relaxation and sets the stage for a restful night’s sleep.

Sleep Peptide Effects

Sleep enhancement

Now, most of these findings are in animal studies…

We’ll visit human sleep research further on… so don’t get all “uppity” with me about rat brain studies.

Improvement of sleep quality

Delta sleep inducing peptide’s gentle touch breathes life into our dreams, fostering a deep and restorative sleep experience. In one study, Delta sleep inducing peptide increased the percentage of slow-wave sleep by 32% and an increase sleep time by 72% in rats (Gottesmann et al., 1982).

Effects on sleep latency and duration

Our sleep maestro not only improves the quality of our rest, but it also impacts how quickly we drift off and how long we stay asleep. In a study involving insomniac patients, Delta sleep inducing peptide administration reduced sleep latency by an average of 22 minutes (Anderer & Saletu, 1991).

Stress and anxiety reduction

Delta sleep inducing peptide has “non sleep effects” and I would even invite the scientific community to interpret DSIP also as “Da Stress Inhibiting Peptide” as shown below:

Anti-stress properties

Our molecular stress-buster wields the power to quell the cacophony of cortisol and other stress hormones, restoring harmony to our bodies. In a study on rats, Delta sleep inducing peptide decreased plasma corticosterone levels by 30% (Kovalzon et al., 1997).

Anxiolytic effects

Like a soothing balm, Delta sleep inducing peptide’s gentle touch alleviates the gnawing grip of anxiety. In a study on mice, Delta sleep inducing peptide demonstrated an anxiolytic effect, reducing anxiety-like behavior in the elevated plus-maze test (Shekunova et al., 2002).

Possible neuroprotective effects

Delta sleep inducing peptide’s enchantment may stretch even further, as it is whispered to possess the power to shield our delicate neurons from harm.

Potential role in neurodegenerative diseases

There are murmurs of Delta sleep inducing peptide’s potential to protect our brains from the ravages of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. Experimental data in this area is still limited, and more research is needed to confirm its neuroprotective effects.

The mechanism for this has been observed in rat brain mitochondria.

In this study, brain metabolism after Delta sleep inducing peptide administration showed less signs of oxidative stress.

Effects on memory and cognitive function

Delta sleep inducing peptide’s gentle caress may also bolster our memories and cognitive abilities, nurturing the delicate workings of our minds. In a study on rats, Delta sleep inducing peptide administration improved memory retention in a passive avoidance task (Badretdinov et al., 1995).

Other physiological effects

The mysteries of DSIP’s powers continue to unfold, revealing a treasure trove of physiological gifts.

Impact on pain perception

DSP has a potent antinociceptive effect which is a fancy way of saying it reduces pain. 

In a study on rats, DSIP demonstrated an analgesic effect, increasing the threshold for pain response (Gyermek et al., 1981).

As such, DSIP could be helpful for patients with pronounced pain episodes.

Effects on hormonal regulation

DSIP’s talents extend to the realm of hormonal regulation, as it has been known to influence the delicate balance of hormones within our bodies. In a study on rats, DSIP administration reduced luteinizing hormone levels by 42% (Ivell et al., 1984).

Potential Therapeutic Applications

As the secrets of DSIP continue to unveil, its soothing touch holds the promise of reprieve for those tormented by various afflictions.

Sleep inducing DSIP – Insomnia and sleep disorders

For those lost in the shadows of sleepless nights, DSIP may offer relief for patients suffering with insomnia. 

In a double-blind study with a placebo group, chronic insomniac patients administered with a DSIP analogue experienced a reduction in sleep latency by an average of 22 minutes, suggesting its potential as a therapeutic agent for severe chronic insomnia patients(Anderer & Saletu, 1991). 

Anxiety and stress-related disorders

DSIP’s calming presence may extend a helping hand to those grappling with the clutches of anxiety and stress.

In animal studies, DSIP demonstrated anxiolytic effects, reducing anxiety-like behavior in mice (Shekunova et al., 2002), and lowering plasma corticosterone levels in rats (Kovalzon et al., 1997). These findings hold promise for the development of therapies aimed at alleviating the burden of stress and anxiety disorders, offering a beacon of hope for depressed patients.

Neurodegenerative diseases

While experimental data is still limited, DSIP’s potential role in protecting the brain from the ravages of diseases such as Alzheimer’s and Parkinson’s warrants further exploration. As researchers continue to delve into the mysteries of DSIP, the peptide may reveal hidden gifts that could aid in the development of novel therapies for these devastating conditions.

Human Sleep – Current Research and Clinical Trials

Like I said above, most of the effects on sleep have been gleaned only from animal models.

Research in humans is a bit less impressive

Clinical trials in humans

• A 1981 double-blind study found that chronic insomniac patients found that subjects slept 59% more, shorter sleep latency, and higher sleep efficiency (Schneider 1981)
• A 1987 double-blind study did not find any statistically significant changes in sleep structure as measured by REM sleep, NREM sleep, or total sleep time (Debellis 1987)
• A 1992 double-blind study in 14 chronic insomnia patients found higher sleep efficiency and subjectively estimated tiredness decreased to similar levels of healthy subjects in 7 nights of injections (Schneider 1992)

There are some limitations to these studies however.

• They measured subjective sleep quality more than objective sleep quality
• They subjectively estimated tiredness
• Sleep structure was not fully characterized by polysomnography in all studies
• Data analysis suggested some observed changes were due to issues with the placebo group

What is promising about these findings is that statistically significant effects were found in such small sample sizes. This indicates that the effects of DSIP were quite large to be detected.

Overall, it seems that DSIP can help correct bad sleep patterns seen in insomnia.

Ongoing clinical trials and future research directions

There are currently no registered clinical trials specifically focusing on DSIP.

Why?

Probably because the studies, although promising, were not considered to have any major therapeutic benefit.

Future research directions may include:

• Investigating the safety and efficacy of DSIP in human clinical trials, particularly in the context of sleep disorders, anxiety, and stress-related conditions because of promising effects on emotional and psychological responses.
• Exploring the molecular mechanisms underlying DSIP’s effects, which could pave the way for the development of optimized analogs or targeted therapies.
• Examining DSIP’s potential neuroprotective properties in greater depth, with a focus on its potential role in the prevention or treatment of neurodegenerative diseases.
• Finding more objective sleep quality measures rather than subjective sleep quality to determine is DSIP can provide a major therapeutic benefit

But, lack of current research has not stopped people with an internet connection, a credit card, and awful sleep from trying out delta sleep inducing peptide…

Anecdotal Use of DSIP

It is important to note that these experiences may not be representative of the general population and should be considered with caution. The following are some examples of anecdotal experiences gleaned from online forums and blogs (that I’m not even going to link to):

1. Improved sleep quality: Some users report experiencing deeper, more restful sleep following DSIP administration. These individuals often describe feeling more refreshed upon waking, with some even noting a decrease in the frequency of nighttime awakenings. And many state DSIP can induce sleep rather quickly.
2. Reduced anxiety and stress: Several anecdotal accounts suggest that DSIP has great stress-protective potency. Some users have described feeling calmer and more relaxed after using the peptide, with a noticeable reduction in racing thoughts and tension.
3. Vivid dreams: A number of users have reported experiencing more vivid, memorable dreams while using DSIP. These individuals often describe a heightened sense of dream recall and an increase in the frequency of lucid dreams.
4. Mixed results: It is important to recognize that individual experiences with DSIP can be quite varied. While some users report positive outcomes, others have found the peptide to have little or no effect on their sleep, anxiety, or stress levels.

What is comfortable about these findings is that they corroborate the research findings.

For the people who report benefits from DSIP, they report:

• Subjective sleep quality improves 
• Subjective tiredness decreases 
• Shorter sleep latency
• Sleep disturbance reductions

Many people praise that DSIP is one of the most powerful sleep promoting substances you can get…

Whereas others feel it was a waste of money.

In conclusion, your mileage with DSIP may vary. 

So, you need to consider the possible side effects before diving into DSIP.

Possible Side Effects and Safety Considerations

Let’s weigh the potential benefits of DSIP against its possible risks and side effects, ensuring the safety and well-being of those who may seek its solace.

Common side effects of DSIP

While limited human studies have been conducted on DSIP, the available literature suggests that it is generally well-tolerated. Some common side effects that have been reported in the existing research include:

• Mild injection site reactions (e.g., redness, swelling, or pain)
• Nausea
• Occasional headaches

It is important to recognize that individual responses to DSIP may vary, and some people may experience side effects not listed here.

Potential risks and contraindications

Given the limited understanding of DSIP’s mechanisms and effects in humans, certain risks and contraindications must be taken into consideration:

• Unknown long-term effects: The long-term safety of DSIP has not been well-established, and the potential risks associated with chronic use remain unclear.
• Interactions with medications: The potential for DSIP to interact with medications has not been extensively studied, so caution is advised when combining DSIP with other substances, particularly those with sedative or anxiolytic effects.
• Pregnancy and lactation: The safety of DSIP use during pregnancy or lactation has not been established, and it is generally recommended that pregnant or breastfeeding individuals avoid its use.
• Individual health conditions: People with pre-existing health conditions or those taking medications should consult with their healthcare providers before using DSIP, as its effects may vary across different populations.

Safety concerns and precautions

To minimize potential risks and ensure the safe use of DSIP, several precautions should be observed:

• Dosing and administration: Users should adhere to the recommended dosing guidelines and administration methods provided by researchers or healthcare professionals.
• Quality and source: As with any peptide, it is crucial to obtain DSIP from reputable sources to ensure product quality and purity.
• Monitoring and reporting: Users should closely monitor their symptoms and report any unexpected or concerning side effects to their healthcare providers or local regulatory agencies.

In summary, while DSIP holds promise as a therapeutic agent for various conditions, its potential side effects and safety considerations must be taken into account. Further research is needed to establish a comprehensive understanding of DSIP’s safety profile and to provide clear guidelines for its responsible use.

DSIP Supplementation and Dosage

As interest in the potential benefits of DSIP grows, it is important to understand the different forms of supplementation, recommended dosage, and factors to consider when using DSIP supplements.

Forms of DSIP supplementation

DSIP is typically available in the form of a lyophilized (freeze-dried) powder, which must be reconstituted with sterile water or bacteriostatic water before administration (you may or may not need a chemistry degree to use this). 

The reconstituted solution can then be injected subcutaneously or intramuscularly, depending on individual preferences and recommendations from healthcare professionals.

Some companies have also developed oral and transdermal formulations of DSIP, although their efficacy and bioavailability compared to injectable forms have not been well-established.

Recommended dosage and administration

As clinical research on DSIP is still limited, definitive dosing guidelines have not been established. 

Now, I’m going to share some dosages with you that I found from “the internet”

And by internet, I mean online forums… not published literature.

Proceed at your own risk and talk to your licensed healthcare provider about this.

And, of course, this is all provided for information purposes only (in case you get asked about this on Jeopardy):

• Dosage: A common starting dose for DSIP is between 100 and 200 mcg per administration, with some individuals titrating up to 400 mcg or more depending on their response and tolerance.
• Frequency: DSIP is typically administered once per day, 30-60 minutes before bedtime, to maximize its sleep-enhancing effects. For those using DSIP to manage stress or anxiety, it may be administered during the day as needed.
• Duration of use: The optimal duration of DSIP supplementation varies among individuals and depends on the desired outcomes. Short-term use (1-2 weeks) may be sufficient for some, while others may require longer periods (4-6 weeks or more) to achieve their goals.

It is essential to consult with a healthcare professional before starting DSIP supplementation to determine the most appropriate dosage and administration schedule for your specific needs.

Factors to consider when using DSIP supplements

When contemplating the use of DSIP supplements, several factors should be taken into account:

• Quality and purity: Obtain DSIP from reputable sources to ensure the highest quality and purity of the product. This will help minimize the risk of contamination or adverse effects.
• Individual response: As with any supplement, individual responses to DSIP may vary. Monitor your symptoms and adjust the dosage or administration schedule accordingly, under the guidance of a healthcare professional.
• Potential interactions: Be aware of the potential for DSIP to interact with medications or other supplements, particularly those with sedative or anxiolytic effects. Consult with your healthcare provider to minimize the risk of adverse interactions.
• Safety and side effects: Pay close attention to any side effects or safety concerns that may arise during DSIP supplementation, and report any unexpected or concerning symptoms to your healthcare provider.

By considering these factors and following the guidance of a healthcare professional, you can make informed decisions about DSIP supplementation and work towards achieving your health and wellness goals.

My Take on DSIP as a Sleep Exert and Physician

Don’t go ordering “internet peptides” just yet!

As we’ve found, just because this has “sleep” in the name doesn’t mean it’s a panacea for your awful sleep.

I know you may be struggling with sleep deprivation or chronic insomnia, but let’s have a short chat, shall we?

DSIP is a very fancy band-aid for sleep issues.

Yes, you may have some success with it…

But at what cost?

Peptides are a story of short-sighted gain with short-term treatment without consideration for the long-term effects.

If you want to get to the root of the issues, stick with me.

It’s rather interesting that DSIP is found in every organ system.

Could that suggest DSIP is involved in a very important system in your body?

(yes)

That’s why DSIP has so many non sleep effects like its ability to normalize blood pressure.

For its systemic effects, DSIP is very similar to melatonin in that regard.

Melatonin is a sleep hormone that is also found in nearly every organ system in the body.

Why is that?

Because both of these compounds exert effects on your circadian rhythm 

Your circadian rhythm is what orchestrates every single biological process in your body, especially sleep.

So, when your rhythm is off, your body will not properly coordinate sleep and then you’ll be out here searching for injectable silver bullets.

That’s why we teach our clients about how their circadian rhythm is essential to not only their sleep but also to every single system in their body.

If you want to learn more about this huge piece of the puzzle, then make sure to check out our free masterclass here: https://optimalcircadianhealth.com/class/

Here’s to sustainable sleep and health!

Sincerely,

Dylan Petkus, MD

References:

• Monnier, M., Dudás, B., & Prochiantz, A. (1977). Sleep-inducing factor: a neuropeptide?. Nature, 268(5616), 152-153.

• Kastin, A. J., & Akerstrom, V. (2003). Delta sleep-inducing peptide (DSIP): a still unresolved riddle. Journal of Neurochemistry, 84(6), 1116-1122.

• Schoenenberger, P., Monnier, M., & Gaillard, R. C. (1988). Delta sleep-inducing peptide: structure-function relationships. Peptides, 9(Suppl 1), 91-95.

• Siva Sankar, D. V., & Swathi, M. (2013). Delta sleep-inducing peptide: a brief review. International Journal of Pharmacy and Pharmaceutical Sciences, 5(2), 34-36.

• Badretdinov, D., Kalimullina, L., & Zefirov, A. (1995). Effects of delta sleep-inducing peptide on learning and memory processes in rats. Bulletin of Experimental Biology and Medicine, 120(9), 1044-1047.

• Gottesmann, C., Gandolfo, G., Zouikr, I., & Lachapelle, F. (1982). Effects of delta sleep-inducing peptide (DSIP) and its analogues on sleep-waking pattern in the rat. Pharmacology Biochemistry and Behavior, 16(6), 913-916.

• Gyermek, L., Soyka, L. F., & Schally, A. V. (1981). Analgesic and morphine antagonist activity of a delta sleep-inducing peptide analog. Proceedings of the Society for Experimental Biology and Medicine, 167(2), 283-286.

• Ivell, R., Richter, D., & Balvers, M. (1984). Delta-sleep-inducing peptide causes a selective reduction of luteinizing hormone secretion in the rat. Neuroendocrinology, 39(2), 96-100.

• Kovalzon, V. M., Moiseeva, Y. G., & Ponomarenko, A. A. (1997). Delta sleep-inducing peptide decreases the level of corticosterone in the plasma of rats. Bulletin of Experimental Biology and Medicine, 124(9), 835-837.

• Shekunova, E. V., Vinogradova, D. V., Dolgintsev, M. E., & Zolotarev, Y. A. (2002). Anxiolytic activity of delta-sleep-inducing peptide in the elevated plus-maze test in mice. Bulletin of Experimental Biology and Medicine, 134(3), 251-253.

• Schneider-Helmert D. Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behavior in severe chronic insomnia. Eur Neurol. 1987;27(2):120-9. doi: 10.1159/000116143. PMID: 3622582.

• Monti JM, Debellis J, Alterwain P, Pellejero T, Monti D. Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs. Int J Clin Pharmacol Res. 1987;7(2):105-10. PMID: 3583493.

• Schneider-Helmert D, Gnirss F, Monnier M, Schenker J, Schoenenberger GA. Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior. Int J Clin Pharmacol Ther Toxicol. 1981 Aug;19(8):341-5. PMID: 6895513.

Ah, sleep. That elusive, dreamy state where we recharge our batteries and escape the hustle and bustle of daily life. 

But what if catching those precious Zzz’s is more like playing a game of hide-and-seek? 

Enter L-Theanine, a natural compound that might just be the sleep fairy you’ve been searching for! 

But is it a dream come true or a nightmare in disguise? 

By the end of this blog, we’ll answer these burning questions and more:

• What is L-Theanine, and where does this natural sleep aid come from?
• How does L-Theanine work its sleep-inducing magic?
• Can taking L-Theanine really help? 
• Is this a safe natural sleep aid?
• How does L-Theanine stack up against other sleep aids on the market for better sleep?
• Can you incorporate L-Theanine into your bedtime routine to finally get the sleep you deserve?
• And, how can you get quality sleep without all these supplements?

Let’s dive into L-theanine! (No sheep were harmed in the making of this blog post.)

What is this Amino Acid from Green Tea?

So, what exactly is L-Theanine? Picture it as a friendly little molecule that loves nothing more than to hang out in tea leaves and spread relaxation vibes.

But don’t be fooled by its chill demeanor—this tiny amino acid packs a powerful punch! In scientific terms, L-Theanine is:

An amino acid (the building blocks of proteins) that occurs naturally in certain plants, primarily:

• Green tea from leaves or commercial tea samples
• Black tea
• Some species of mushrooms

It’s like a hidden treasure in your teacup, just waiting to help you unwind. 

Amino acids often have a biological effect. 

As an amino acid L-theanine exerts its effect on nerve cells by interacting with receptors and modifying biochemical pathways.

Now, L-Theanine isn’t just confined to the world of tea leaves and mushrooms.

itIt’s also available as a supplement, for those who want to harness its relaxation powers without sipping on a cuppa. (No teapots were harmed in the making of these supplements!)

But why, you might ask, are we so interested in this particular amino acid? 

Well, it turns out that L-Theanine has a knack for promoting relaxation, which could be just the ticket for those struggling. 

Here’s a quick rundown of what makes L-Theanine helps with so special:

• It can help increase relaxation without causing drowsiness (Nobre, Rao, & Owen, 2008)
• It may improve focus and mental alertness (Haskell, Kennedy, Milne, Wesnes, & Scholey, 2008)
• It can potentially reduce stress and anxiety (Lu, Gwee, Ho, & Moochhala, 2004)

Sounds pretty dreamy, right? 

But how does it actually work its magic?
(and… are there other ways to make this magic happen?) 

Hold onto your teacups, friends, because we’re about to dive into the science behind it in the next section.

How it Works

Let’s explore how L-Theanine works its magic!

L-Theanine targets the brain:

L-Theanine is like a VIP guest at the brain’s relaxation party. It crosses the blood-brain barrier with ease, allowing it to interact directly with our brain cells (Nathan et al., 2006). Talk about an exclusive invitation!

Effect on neurotransmitters:

Once inside the brain, L-Theanine gets to work on our neurotransmitters, which are like the brain’s communication with central nervous system. It has a few tricks up its sleeve:

• Boosts levels of GABA, a calming neurotransmitter (Yoto et al., 2012)
• Increases dopamine, which plays a role in pleasure and reward (Yamada et al., 1999)
• Influences serotonin, which helps regulate mood (Yamada et al., 1999)

All these actions work together like a well-orchestrated dance of calming brain chemicals, helping to create a sense of relaxation.

Impact on stress and anxiety:

L-Theanine doesn’t stop there! It also tackles stress and anxiety head-on like a fearless superhero. 

L-theanine does this by:

• Reducing the release of the stress hormone cortisol (Kimura et al., 2007)
• Blocking the effects of glutamate, an excitatory neurotransmitter (Kakuda et al., 2002)

So, not only does L-Theanine help us relax, but it also keeps stress and anxiety at bay. 

However, remember, there is no “free lunch” in supplement-world.

I have a bit of a golden rule “if thou make it, thou shall (probably) not take it”

Why is that?

Whenever you ingest a substance (like all these “brain chemicals”) that your human body already makes naturally, you reduce your own ability to make it.

That is, you become dependent on it while becoming more resistant to it (that means the dose needs to go up).

So keep that in mind as we continue…

Now that we’ve unraveled the mysteries of L-Theanine’s inner workings, let’s explore its connection to healthy sleep.

Sleep Quality

L-theanine works its magic through two processes… and you need to understand these before just slapping this supplement into your Amazon cart. 

First, it promotes relaxation and alpha brain waves. 

Alpha brain waves are when your mind goes into a “wakeful relaxation” mental state and promotes relaxation (Rao et al., 2015).

Right before you go to bed, your brain waves are in a “beta” state which is more active.

When calming brain chemicals enter the fray, then your beta brain waves shift into alpha brain waves.

Alpha waves are required to enter the first stage of sleep.

Thus, it induces alpha waves to help you fall asleep.

But, wait! There’s more.

If you act now I’ll throw in 3 sham-wows

Not only does it help you relax into sleep, but it also enhances the quality.

In fact, the research has found that L-theanine:

• Improved quality in 67% of participants (Rao et al., 2015). 
• Reduces sleep latency by an average of 9.9 minutes (Rao et al., 2015). (sleep latency is how long it takes to fall asleep; this is also known as sleep onset)
• Keeps you snoozing like a baby, tucked in for a longer, uninterrupted sleep (Ota et al., 2015).
• Increased duration by an average of 17.3 minutes per night (Rao et al., 2015). 💤
• Boosts REM sleep and improves NREM sleep, the stage where dreams happen and repairs, respectively, 20% in a study (Ota et al., 2015). 
• Reduced nighttime awakenings by 58% (Rao et al., 2015). (Morning, sunshine! ☀️)

But wait! (There’s even more; okay I’ll stop)

Before you start sipping L-theanine-infused tea, let’s explore the next chapter on side effects!

Potential Side Effects and Concerns

Let’s delve deeper into the world of side effects and concerns related to L-theanine.

The general safety of L-Theanine

What the heck is “general safety” anyway?

This term refers to the rather archaic way the FDA will classify things as “probably won’t kill you” vs “might kill you”

L-Theanine has been demonstrated to be safe for consumption (Nobre et al., 2008) and the FDA has it as “generally recognized as safe” (GRAS).

Possible side effects of L-Theanine

Although L-Theanine is considered safe, some individuals may experience side effects such as:

• Headaches
• Dizziness
• Gastrointestinal issues

Let’s break these down one by one.

Headaches

• A study by Kimura et al. (2007) found that some participants reported headaches as a side effect of L-Theanine intake.
• However, the overall incidence of headaches was low and not statistically significant compared to the control group.

Dizziness

• In the same study by Kimura et al. (2007), a few participants experienced dizziness after consuming L-Theanine.
• Similar to headaches, the occurrence of dizziness was not significantly different from the control group, indicating that it may not be a common side effect.

Gastrointestinal issues

• Gastrointestinal issues were also reported by some participants in the study conducted by Kimura et al. (2007).
• The study did not find a significant difference between the L-Theanine and control groups, suggesting that gastrointestinal issues may not be a prevalent side effect.

Now, remember what I said above about no “free lunches?”

When you use a substance like L-theanine for sleep support or to relax, you’re reducing your body’s own natural ability to do the same.

Don’t get me wrong, L-theanine is a good short-term solution, but you also need a long-term solution to get to the real issues underneath.

Overall, L-theanine seems to be pretty safe in isolation.

But how does it play with others?

Interactions with medications and other sleep aids

L-Theanine can have interactions with certain medications and sleep aids. Some examples of medications that might have interactions with L-Theanine include:

• Antihypertensive (blood pressure) medications: L-Theanine may low blood pressure too much alongside blood pressure medications, which could cause excessive reductions in blood pressure (Rogers et al., 2008).

• Stimulant medications: L-Theanine may counteract the stimulating effects of medications such as amphetamines or methylphenidate, potentially reducing their effectiveness (Nobre et al., 2008).

• Sedatives and other sleep aids: L-Theanine may enhance the effects of sedatives or sleep aids, increasing the risk of excessive sedation or drowsiness (Turkozu & Sanlier, 2017).

It is essential to consult your healthcare provider before combining L-Theanine with other medications or sleep aids to avoid potential adverse effects!!!

The importance of L-Theanine Dosage 

So, how much L-theanine?

Here are the dosage considerations: 

• For stress reduction and anxiety: 100-200 mg of L-Theanine, one to two times per day, has been reported to be helpful in reducing stress and anxiety in some individuals (Kimura et al., 2007).
• Stress related symptoms go down with l-theanine administration because it biochemically counteracts all the stress hormones throughout your body.
• For sleep: 200-400 mg of L-Theanine, taken 30-60 minutes before bedtime, may improve quality and  duration (Rao et al., 2015).

Please note that these are general guidelines and individual responses may vary. 

When taking L-theanine you need to monitor for any symptoms and how you feel.

And, if you are taking L-theanine, make sure to consult your healthcare provider for personalized dosing recommendations.

Now, you may be second-guessing L-theanine and perhaps even regretting that you already ordered it on Amazon (heck, maybe it’s already at your door…)

Comparing L-Theanine to Other Sleep Aids

To help you make the best decision possible, let’s do some comparisons.

We’ll do:

• Prescription medications vs. L-theanine
• Natural Remedies vs. L-theanine

L-Theanine Benefits vs Drawbacks:

• Benefits:
• L-Theanine is a natural substance found in green tea leaves, making it a more natural alternative to prescription medications (Nobre et al., 2008).
• It has been shown to improve sleep quality and duration without causing dependency or significant side effects (Rao et al., 2015).
• L-Theanine may also help reduce stress and anxiety, further improving sleep quality (Kimura et al., 2007).
• Drawbacks:
• L-Theanine may not be as potent as prescription sleep medications for individuals with severe insomnia or sleep disorders (Rao et al., 2015).
• The optimal dosage and long-term effects of L-Theanine have not been thoroughly researched, so its efficacy and safety over extended periods are not well-established (Turkozu & Sanlier, 2017).

Prescription Sleep Medication Benefits vs. Drawbacks

• Benefits:
• Prescription sleep medications can be highly effective for treating severe insomnia and sleep disorders, providing faster and more reliable results than L-Theanine (Roth, 2007).
• They are often prescribed in a controlled manner under the supervision of a healthcare provider, which can help ensure proper dosing and monitoring for side effects (Roth, 2007).
• Drawbacks:
• Prescription sleep medications can cause dependency, leading to difficulties in discontinuing their use and potential withdrawal symptoms (Roth, 2007).
• They may have more severe side effects compared to L-Theanine, such as drowsiness, dizziness, and impaired cognitive function (Turkozu & Sanlier, 2017).
• Prescription Medications 

• Drowsiness
• Dizziness
• Dry mouth
• Gastrointestinal issues (nausea, constipation, diarrhea)
• Cognitive impairment (memory issues, difficulty concentrating)
• Dependency and withdrawal symptoms

Obviously, I’m not going to go all “internet doctor” on you and tell you what’s best for you.

But, overall, prescription medications will have more side effects as a trade-off for being more heavy-handed.

And, L-theanine might be “too weak” for you if your sleep is royally screwed up.

Either way, I think you’ll enjoy diving into the deeper issues in a bit.

Natural sleep remedies vs. L-Theanine

Melatonin

• Benefits:
• Melatonin is a hormone naturally produced by the body that can help promote sleep by regulating the sleep wake cycles (Arendt, 2005).
• Melatonin supplementation may be effective in treating insomnia, jet lag, and circadian rhythm sleep disorders (Auld et al., 2017).
• It is available over the counter and considered a safe and non-addictive sleep aid, with few side effects when used appropriately (Auld et al., 2017).
• Drawbacks:
• Melatonin may not be effective for everyone, and its efficacy can vary depending on individual factors, such as age and the underlying cause of issues (Arendt, 2005).
• Improper dosing or timing of melatonin supplementation can lead to disrupted patterns and daytime drowsiness (Auld et al., 2017).

Valerian Root

• Benefits:
• Valerian root is a herbal supplement that has been traditionally used for its sedative and anxiolytic effects, which promotes relaxation and help promote sleep (Bent et al., 2006).
• It is in the class of GABA supplements (also known as Gamma-Aminobutyric Acid). One can get GABA from a dietary supplement like Valerian, or by itself in a pure supplement form.
• Some studies suggest that valerian root may be effective in treating mild to moderate insomnia without causing dependency or significant side effects (Fernández-San-Martín et al., 2010).
• Drawbacks:
• The evidence supporting the efficacy of valerian root for sleep improvement is inconclusive, with some studies showing no significant benefits compared to a placebo (Bent et al., 2006).
• The optimal dosage and long-term safety of valerian root are not well-established, and the quality of valerian root products can be inconsistent (Fernández-San-Martín et al., 2010).

Chamomile

• Benefits:
• Chamomile is a popular herbal tea that has been used for centuries to promote relaxation and sleep (Srivastava et al., 2010).
• Some studies suggest that chamomile may have mild sedative effects, which could help facilitate sleep quality and reduce the time it takes to fall asleep (Zick et al., 2011).
• Drawbacks:
• The evidence supporting the efficacy of chamomile for sleep improvement is limited and requires further investigation to establish its effectiveness (Srivastava et al., 2010).
• Chamomile may not be as potent as other natural remedies or prescription sleep medications for individuals with severe insomnia or sleep disorders (Zick et al., 2011).

L-Theanine vs. Melatonin, Valerian Root and Chamomile

This is the most “apples to oranges” comparison you could make (and I’m only doing it for SEO purposes… there I admitted it!)

Nonetheless, here’s some truth for you.

Each substance will work on a different biochemical pathway.

Both l-theanine and the other aids may have success for you.

That is, either l-theanine or something else on the above list could help out.

But!

You may have success with NONE of them.

Now, the real question shouldn’t be “Which sleep supplement is best?”

The real question is “Why do I need sleep supplements in the first place?”

How to Incorporate L-Theanine into Your Routine

Now, you can start to tell I “kinda-like-but-don’t-love” L-theanine.

So, I don’t want to leave anyone hanging on understanding how people typically use it.

Recommended Dosage and Timing

Dosage: Although the optimal dosage of L-Theanine for sleep improvement is not well-established, studies have generally used doses ranging from 100 to 400 mg per day (Rao et al., 2015). 

It’s important to start with a lower dose and gradually increase it as needed, keeping in mind that individual responses may vary.

Timing: L-Theanine should be taken about 30 minutes to 1 hour before bedtime to allow enough time for the relaxing effects to occur (Rao et al., 2015). It can also be taken during the day to help manage stress and reduce anxiety too, which can contribute to better sleep quality at night.

Many times, one can dial in the dose with an L-theanine mixture or powder that can easily change the dose.

Finding a High-Quality Supplement

To ensure that you are receiving the maximum benefits supplements, it is crucial to choose a high-quality supplement. Here are some tips for finding a reliable product:

1. Reputable Brand: Select a supplement from a well-known and reputable brand with a history of producing high-quality and safe products.
2. Third-Party Testing: Look for products that have been independently tested and verified by a third-party organization, such as NSF International or USP, to ensure the product’s purity, potency, and safety.
3. Product Label: Examine the product label carefully to confirm the type of L-Theanine used, the dosage per serving, and any additional ingredients. Avoid products with unnecessary fillers or additives.
4. Consult a Healthcare Professional: Speak to your doctor or pharmacist for personalized advice on choosing the right L-Theanine supplement based on your specific needs and health status.

Now, you have a choice, young grasshopper…

You could totally take L-theanine and feel some improvements for a bit… or, ye chosen one, could choose to deal with the deeper issues underneath!

Learn more about what does l theanine do.

Addressing the Root Issue

The real issue is with your mitochondria which are the energy-producing structures inside your cells (powerhouse of the cell…)..

Poor mitochondrial function leads to sleep disturbances for 3 big reasons:

1. Not enough energy is produced to allow the energetic-expensive process of sleep to actually work
2. Mitochondria also produce melatonin (your sleep hormone)
3. Mitochondria are important to allow your neurons to detox at night to improve sleep efficiency

That’s why when you fix your mitochondria then you fix your sleep!

To help you optimize your mitochondria, I’d like to invite you to our masterclass on mitochondria here: https://optimalcircadianhealth.com/class

The free masterclass will show you the deep connection between your mitochondria and sleep. 

Thanks for joining me; here’s to your sleep!

• References:

  • Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A., & Scholey, A. B. (2008). The effects of L-theanine, caffeine, and their combination on cognition and mood. Biological Psychology, 77(2), 113-122.
  • Lu, K., Gray, M. A., Oliver, C., Liley, D. T., Harrison, B. J., Bartholomeusz, C. F., … & Nathan, P. J. (2004). The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Human Psychopharmacology: Clinical and Experimental, 19(7), 457-465.
  • Nobre, A. C., Rao, A., & Owen, G. N. (2008). L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pacific Journal of Clinical Nutrition, 17(1), 167-168.
  • Kakuda, T., Nozawa, A., Unno, T., Okamura, N., & Okai, O. (2002). Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat. Bioscience, Biotechnology, and Biochemistry, 66(2), 268-271.
  • Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biological Psychology, 74(1), 39-45.
  • Nathan, P. J., Lu, K., Gray, M., & Oliver, C. (2006). The neuropharmacology of L-theanine (N-ethyl-L-glutamine): A possible neuroprotective and cognitive enhancing agent. Journal of Herbal Pharmacotherapy, 6(2), 21-30.
  • Yamada, T., Terashima, T., Okubo, T., Juneja, L. R., & Yokogoshi, H. (1999). Effects of theanine, r-glutamylethylamide, on neurotransmitter release and its relationship with glutamic acid neurotransmission. Nutritional Neuroscience, 2(5), 363-368.
  • Rao, T. P., Ozeki, M., & Juneja, L. R. (2015). In Search of a Safe Natural Sleep Aid. Journal of the American College of Nutrition, 34(5), 436-447. PubMed
  • Ota, M., Wakabayashi, C., Sato, N., Hori, H., Hattori, K., Higuchi, T., … & Kunugi, H. (2015). Effect of L-theanine on glutamatergic function in patients with schizophrenia. Acta Neuropsychiatrica, 27(5), 291-296. PubMed
  • Nobre, A. C., Rao, A., & Owen, G. N. (2008). L-Theanine, a natural constituent in tea, and its effect on mental state. Asia Pacific Journal of Clinical Nutrition, 17(S1), 167-168. PubMed
  • Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biological Psychology, 74(1), 39-45. PubMed
  • Kelly, S. P. (2019). L-Theanine: Properties, synthesis and isolation from tea. Journal of Functional Foods, 58, 180-188. PubMed
  • Arendt, J. (2005). Melatonin: characteristics, concerns, and prospects. Journal of Biological Rhythms, 20(4), 291-303. PubMed
  • Auld, F., Maschauer, E. L., Morrison, I., Skene, D. J., & Riha, R. L. (2017). Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders. Sleep Medicine Reviews, 34, 10-22. PubMed
  • Bent, S., Padula, A., Moore, D., Patterson, M., &Garvin, D. (2006). Valerian for sleep: a systematic review and meta-analysis. The American Journal of Medicine, 119(12), 1005-1012. PubMed
  • Fernández-San-Martín, M. I., Masa-Font, R., Palacios-Soler, L., Sancho-Gómez, P., Calbó-Caldentey, C., & 
  • Flores-Mateo, G. (2010). Effectiveness of Valerian on insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Medicine, 11(6), 505-511. PubMed
  • Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biological Psychology, 74(1), 39-45. PubMed
  • Nobre, A. C., Rao, A., & Owen, G. N. (2008). L-Theanine, a natural constituent in tea, and its effect on mental state. Asia Pacific Journal of Clinical Nutrition, 17(S1), 167-168. PubMed
  • Rao, T. P., Ozeki, M., & Juneja, L. R. (2015). In Search of a Safe Natural Sleep Aid. Journal of the American College of Nutrition, 34(5), 436-447. PubMed
  • Srivastava, J. K., Shankar, E., & Gupta, S. (2010). Chamomile: A herbal medicine of the past with a bright future. Molecular Medicine Reports, 3(6), 895-901. PubMed
  • Turkozu, D., & Sanlier, N. (2017). L-Theanine, unique amino acid of tea, and its metabolism, health effects, and safety. Critical Reviews in Food Science and Nutrition, 57(8), 1681-1687. PubMed
  • Zick, S. M., Wright, B. D., Sen, A., & Arnedt, J. T. (2011). Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia: A randomized placebo-controlled pilot study. BMC Complementary and Alternative Medicine, 11, 78. PubMed

Adrenal fatigue isn’t even real.

But the massive fatigue, brain fog & poor mental clarity, and the slew of other symptoms you experience are real.

If you want to sound like a cool kid, you’d really say hypothalamus-pituitary-adrenal axis dysfunction…

But hey, I’m not here to grill you on the specifics of what to call your adrenal exhaustion.

Either way, we’re going to answer the following questions on adrenal fatigue supplements:

• What are some of the best adrenal support supplements? 
• How can I strengthen my adrenal glands naturally?
• Does Ashwagandha help with adrenal fatigue?
• What vitamin deficiency causes adrenal fatigue?
• How do you know if you need adrenal supplements?
• Should you take adrenal supplements?

If you’re experiencing adrenal fatigue (not adrenal insufficiency… that’s very different), then buckle up, buttercup.

Let’s dive into adrenal health and unlock the secrets to a happier, more energetic you. Life’s too short to feel like a deflated balloon.

Next up: adrenal fatigue and its sneaky ways.

Understanding Adrenal Fatigue

Alright, folks, let’s talk adrenal fatigue. Imagine your adrenal glands as tiny, hardworking employees in the Stress Response Department of your body. 

When they’re overworked, they can’t keep up with the demands (hello, burnout!). 

Although conventional medicine will deny its existence (Cadegiani & Kater, 2016), there are very real mechanisms for adrenal fatigue to happen..

Here’s the breakdown

• Your body’s stress response revs up with acute stress
• Adrenals pump out more stress hormones
• This puts your cells into overdrive
• This wears down your cells…
• Which raises your body’s stress levels, even more,
• Which triggers your adrenals…

Unfortunately, this is how your body responds to long periods of chronically high stress levels which produces some nasty symptoms.

Adrenal fatigue symptoms 

Some of the sneaky symptoms you might experience:

• Difficulty waking up
• Salt cravings
• Sugar cravings
• Insulin resistance
• Brain fog / bad mental clarity
• Low energy levels (think of a sloth on a slow day)

Now, we’ll also cover how these symptoms are also… kinda… not really adrenal fatigue at all.

These are all related to your mitochondria!

If your mitochondria aren’t producing energy, then physical and mental fatigue settles in.

Your sleep requires mitochondria to function properly, hence sleep doesn’t do jack for you and you may have to turn to sleeping pills.

And, your mitochondria allow your proteins to retain salt inside of cells… so when that’s off electrolytes go right through you and you’re constantly craving salt.

So what’s causing this?

Causes of Adrenal Fatigue

So, what’s causing these tiny troopers to struggle? Some common culprits include:

• Poor diet
• Insufficient sleep (Vgontzas et al., 2001)
• Over-exercising (Meeusen et al., 2007)
• Toxins or infections

And again, I want you to start thinking about how these all fit together without considering your adrenals…

Well, I can also just tell you.

All of these will destroy your mitochondria.

If you put bad fuel in your metabolic engines, they’ll break down faster just like if you put diesel into your car.

If you don’t recharge your batteries, then the damage is done (just like your laptop battery)

And, while we’re on the computer analogy…

If you keep letting things assault your circuitry from toxins to viruses, then your mitochondria short-circuit and can’t produce as much energy as they need to.

And remember, when your mitochondria aren’t working right, then your adrenals have to step in to squeeze more juice out of your sun-dried semi-ash lemons. 

Chronic Stress and Adrenal Fatigue

Remember, your adrenal glands are your body’s stress bouncers. When stress piles up like dirty laundry, they’re working overtime to keep up with the stress response. 

But sometimes, they just can’t handle the load. That’s where chronic stress comes into play (Lennartsson et al., 2015).

Chronic stress is like a never-ending roller coaster. Your adrenal glands are constantly producing cortisol, the stress hormone, to help you cope. But even the toughest bouncers need a break! (Hence, why reducing stress is critical)

Over time, they become worn out and can’t produce enough cortisol to keep up with the demand (Cadegiani & Kater, 2016).

Now, chronic stress is simply when your nervous system puts your mitochondria into overdrive which essentially fries their energy production and shuts you down as a protective mechanism.

This is why stress related fatigue is a serious issue.

You see, we’re going to talk a lot about adrenals here today… but if we ignore the mitochondria then you’ll be chasing supplements and information like this for years.

Think of your adrenals as the weak link in the chain that breaks when you have poorly functioning mitochondria.

So, let’s focus on this weak link next.

The Role of Adrenal Glands and Hormones

Let’s zoom in on adrenal glands and hormones, shall we? 

For starters, your pituitary gland will stimulate your adrenal glands ability to produce hormones.

And, your adrenal glands produce many hormones we’ll discuss down below.

They do a bit more than just regulate cortisol production and manage stress.

Adrenal glands function

Picture your adrenal glands as tiny factories that produce hormones needed to keep your body in tip-top shape. 

This hormone production is the primary function of your adrenals

However, when this goes haywire… your adrenals can become a supervillain with stress hormones taking over. 

Hormones produced by adrenal glands: cortisol, adrenaline, and others

These hormone heroes include:

• Cortisol (the stress manager)
• Adrenaline (the energy booster)
• Aldosterone (the salt balancer)
• DHEA (the hormone balancer)

Cortisol is our primary stress hormone (Tsigos & Chrousos, 2002). 

Cortisol production amps up your central nervous system and bumps up your blood sugar levels too.

We’ve already beaten the cortisol horse dead, let’s move on to other stress hormones.

Adrenaline

Adrenaline, on the other hand, kicks in when we need a burst of energy (like running from a zombie horde!). 

Think of cortisol levels as caffeine and adrenaline is like espresso inside of a red bull.

Adrenaline is a fast-acting neurotransmitter that brings your nervous system into HYPER drive.

I would argue that most of the damage is from adrenaline rather than cortisol because of the massive shifts in mitochondrial function.

And, adrenaline is responsible for the “wired” feeling that comes along with adrenal fatigue and the anxiety that can skyrocket when life comes crashing down around you.

Aldosterone and Blood Pressure

Aldosterone helps maintain healthy blood pressure by balancing salt and water levels in the body (Funder, 2013).

When aldosterone isn’t working, this is why you get light-headed when you stand up because there isn’t enough blood pressure to maintain blood flow through your blood vessels to your head.

When adrenal fatigue gets pretty bad, then blood pressure is typically low all the time which worsens your fatigue because you’re not getting nutrients and oxygen to your mitochondria.

(Don’t worry, treating your adrenal fatigue won’t give you high blood pressure)

DHEA

Lastly, DHEA keeps our hormones balanced and supports immune function (Kroboth et al., 1999).

Although cortisol and aldosterone are literally required to survive, DHEA is required to THRIVE.

When you’re struggling with adrenal fatigue, DHEA levels go low because your body is diverting all available resources into creating the hormones needed to survive (like DHEA and other hormones from reproductive organs).

(This is very similar to how you have to divert your focus to just get through the day… funny how that works, huh?)

Just like when you’re in survival mode, there is a severe consequence.

DHEA is your body’s primary hormonal anti-oxidant.

So, when DHEA is low, then your cells live in inflammation and this damages your mitochondria even more.

Impact of hormone imbalances on the body

But, when these heroes are out of whack, it’s like a comic book gone wrong. 

Imbalances can lead to:

• Chronic fatigue
• Weight gain
• Sleep issues
• Anxiety and depression
• Weakened immune system

So, how do you keep your hormone heroes in check? 

(Let me give you a little hint… your mitochondria are the first place your hormones are made)

The answer partly lies in taking care of your adrenal glands (remember, they’re the ones running the show!). That means managing stress, eating well, and getting enough sleep.

Stay tuned for our next thrilling adventure: natural ways to strengthen adrenal glands!

Natural Ways to Strengthen Adrenal Glands

Alright, folks, it’s time to flex those adrenal muscles! 

Let’s dive into natural ways to help your body adapt. Ready, set, go!

Stress management techniques

First up, we have stress management. You can’t always avoid stress (unless you’re a Zen master), but you can learn how to deal with it. Here are some techniques:

• Meditation (think of it as a brain massage)
• Deep breathing (inhale the good stuff, exhale the bad stuff)
• Yoga (become a bendy pretzel)
• Laughter (seriously, it’s good for you! (Gross et al., 2004))

Now, these will help calm down your nervous system and prevent further damage… but this does NOT reverse the damage.

Think of this as putting out the house fire… but not renovating the house.

Nonetheless, this will reduce stress related fatigue.

Diet and lifestyle changes

Next on the list: diet and lifestyle changes. Your body is like a fancy car – you gotta put in good fuel to keep it running smoothly. Here’s what you need:

• Whole foods (fruits, veggies, lean proteins)
• Healthy fats (avocado, nuts, seeds, olive oil)
• Low sugar intake (say bye-bye to that sweet tooth)
• Stay hydrated (water, water, and more water)

Again, remember that the issue is in your mitochondria.

Mitochondria are your metabolic engines.

Just like the engine in your car, you can only slow down the breakdown by choosing better fuels.

That is, diet is just a way to slow down the damage, but not fully reverse it.

Importance of sleep and exercise

Last but not least: sleep and exercise. Consider these the dynamic duo of adrenal health.

The health benefits of sleep can’t be ignored, make sure to aim for:

• 7-9 hours a night (your body will thank you)
• Consistent bedtime (routine is key)
• A sleep-friendly environment (cool, dark, and quiet)

Now sleep helps a bit because it will trigger the repair of mitochondria.

However, you also need good mitochondria to have good sleep quality which is why you very likely wake up still feeling like garbage.

The other helpful thing to consider is exercise because it helps reduce stress.

Get moving with:

• Moderate exercise (30 minutes a day is a good start)
• Mix it up (try walking, swimming, or dancing)

However, exercise may not help you.

You need to listen to your body because exercise is a physical stress (don’t push too hard, or you’ll end up with the overtraining blues (Meeusen et al., 2007))

Because if the engines in your car are fuming… you wouldn’t keep driving, right? (I hope not)

You need to repair your engines to get the most out of exercise first.

Now, let’s turn our attention to key vitamins and minerals for adrenal health (dun dun dun!).

Adrenal Fatigue Supplements – Vitamins and Minerals

Let’s dive into some adrenal fatigue supplements related to vitamin and minerals

Vitamin C Supplements (ascorbic acid)

Vitamin C is like the Hulk of antioxidants, protecting your adrenal glands from stress-induced damage with its antioxidant properties (Padayatty et al., 2003). But, even the Hulk can’t fight off everything – sometimes, the stress response drains our vitamin C stores in our adrenal cortex.

How to address it:

• Eat vitamin C-rich foods (hello, oranges and strawberries!)
• 250-500 mg of Vitamin C is a typical dose for supplements for adrenal fatigue (but talk to a doc first)

However, just because vitamin C reduces the damage doesn’t mean it STOPS the damage from happening.

And, the issue with vitamin C is that it may reduce free radicals TOO much.

That’s a problem because your mitochondria actually need SOME free radicals to rebuild and restore balance.

That’s why so many people get hooked on tons of vitamin C or even get IV vitamin C drips just to get through a family vacation.

Vitamin D Supplementation

Vitamin D is like the sun’s fat soluble vitamin gift to our body (literally!). It boosts our mood, supports the immune system, improves bone health, and helps regulate hormones (Holick, 2007). However, we often don’t get enough sunshine, leading to deficiencies.

How to address it:

• 1000-2000 IU is a typical dose for supplements for adrenal fatigue (again, chat with a doc, and include healthy fats and fatty acids to aid in absorption)

Now, I hate vitamin D.

Why?

Because nearly every client we get has been on loads of vitamin D but they still have a vitamin D deficiency. 

Why is that?

Because nobody is asking “why” vitamin D is low in the first place.

Write this down:

Vitamin D is burned in the fire of failing mitochondria.

Bad mitochondria = inflammation = increased vitamin D consumption = no matter how much vitamin D you take you can’t get your levels to where they need to be.

Pantothenic acid (vitamin B5)

Vitamin B5 is the adrenal glands’ BFF. It helps maintain cortisol levels and other adrenal hormones (Rice, 2004). But sometimes, stress can deplete our pantothenic acid levels.

How to address it:

• Chow down on B5-rich foods (avocado, chicken, and sunflower seeds)
• 10-50 mg is a typical dose for supplements for adrenal fatigue (you guessed it – talk to a doc)

And, again, why is B5 low?

This vitamin is used to help convert fuels to be burned up by your mitochondria… especially sugars.

Sugar is your body’s emergency fuel.

So, when your mitochondria are constantly in emergency mode you are going to burn more sugar and thus use up more pantothenic acid.

Other essential vitamins and minerals for adrenal support

Magnesium

Magnesium is like a magician that helps your body relax (Cuciureanu & Vink, 2011). However, your stress response can make this relaxation magician disappear, leaving you magnesium-deficient.

How to address it:

• Munch on magnesium-rich foods (spinach, almonds, and pumpkin seeds)
• 200-400 mg is a typical dose for supplements for adrenal fatigue (but, as always, consult a doctor)

Magnesium is low partly because of insufficient amounts in our foods…

But largely because of the increased carbohydrate burning your cells are forced to do because your mitochondria can’t burn fat.

And, your mitochondria also allows your proteins to retain normal levels of minerals, namely potassium, and magnesium… hence why these minerals are in poor amounts in people with adrenal fatigue.

Zinc

Zinc is a booster for your immune system and immune response, keeping it strong and ready to fight (Haase & Maret, 2003). But your stress response can be like a sneaky thief, stealing your zinc reserves.

How to address it:

• Fill up on zinc-packed foods (oysters, beef, and chickpeas)
• 15-30 mg is a typical dose for supplements for adrenal fatigue (and, you know the drill – check with a doc)

Zinc is an essential nutrient for mitochondrial function because as a metal it allows electrons to bounce from point A to point B in your mitochondria to allow energy to be produced.

Selenium

Selenium is an antioxidant ninja, protecting your adrenal glands from damage (Rayman, 2000). But even ninjas can be defeated, and stress might leave you with low selenium levels.

How to address it:

• Enjoy selenium-rich foods (Brazil nuts, tuna, and eggs)
• 55-200 mcg is a typical dose for supplements for adrenal fatigue (remember to consult a doctor first)

Now, selenium suffers the same limitations of Vitamin C that we discussed.

By addressing these deficiencies, you’ll have a band-aid on your bleeding adrenal glands. 

Adrenal Fatigue Diet

Overall, it’s honestly best to have an “adrenal fatigue diet” that gets all these nutrients from food.

And, other components of an adrenal fatigue diet should include smaller meals that will provide some adrenal support (but cause other issues with your gut and liver function).

This helps short-term by stabilizing your blood sugar.

When your cortisol levels are off, then your blood sugar is off too.

Blood sugar levels determine how much fuel is going to your mitochondria.

Hence, maintaining balanced blood sugar levels will prevent them from falling apart and maintaining your energy levels.

Onward to adrenal herbals!

Supplements to support adrenals (herbals)

Adrenal fatigue supplements are like a team of superheroes, each with unique powers to help your adrenal glands bounce back from stress. But not all heroes wear capes (or come in pill form)!

These herbs are the foundation or alternative medicine like ayurvedic medicine and traditional Chinese medicine.

Overall, these herbs help your body to respond to all the stress response consequences.

Ashwagandha (Withania somnifera)

Ashwagandha does more than just have a calming effect on your mind and cortisol levels (Chandrasekhar et al., 2012). Here’s a closer look at its magical properties:

• Decrease cortisol levels (it’s like a soothing lullaby for your adrenals)
• Help maintain blood sugar
• Boosts brain function, including memory and focus (who needs a thinking cap when you have Ashwagandha?)
• Supports a healthy immune system (like a shield against pesky germs)

However, Ashwagandha’s biochemical effect is akin to vitamin C, meaning it also encounters similar limitations. So while it does help your body deal with stress, it may not be the ultimate solution for adrenal fatigue.

A typical dose of Ashwagandha is 300-500 mg, but remember to consult your wizard – er, doctor – before embarking on this magical journey.

Rhodiola rosea

Rhodiola rosea, the supercharged battery of the plant world, not only energizes you but also helps you adapt to stress (Olsson et al., 2009). Let’s peek under the hood to see how it works:

Acts as an adaptogen, helping your body cope with various stressors (like a personal stress-busting sidekick)

• Enhances physical endurance and mental performance (faster, smarter, stronger – who doesn’t want that?)
• Fights fatigue and increases overall well-being (it’s like a spa day for your cells)

Just like with Ashwagandha, however, it’s important to remember that Rhodiola rosea is not a one-size-fits-all solution for adrenal fatigue.

When considering Rhodiola rosea, a typical dose ranges from 200-600 mg. But don’t forget to ask your friendly doctor for advice!

Now, these two are the top herbals… you will run into an infinite amount of them and I won’t ever be able to cover them all… 

Let’s teach you how to “fish” a bit

How to choose the right supplement for your needs

Whenever my clients ask me “should I take X” I always ask them “what’s your outcome?”

You need to have a process to determine what your needs are and what your outcome is

Generally, do the following:

• Assess your symptoms (are you tired, stressed, or both?)
• Research different herbs (knowledge is power)
• Determine how this could help you achieve your outcome
• Consult your doctor (I’ve said this so many times my lawyer would be proud)
• Set a determinate amount of time for you to see this effect (i.e. in 3 weeks I hope to see improved sleep quality, etc.)

You need a process to trial supplements because, if not, then you end up throwing spaghetti on the wall and never know what does what.

You need a steady hand in guiding your healing journey! 

Don’t make decisions from fear and panic, make them from where you want to be!

What to look for in a high-quality adrenal supplement

Again, I can’t review all 423789 supplements from Amazon

Here are some guidelines you want to follow:

• Trusted brand (you want Iron Man, not Iron “Man”)
• Third-party testing (like a detective ensuring your supplement is legit)
• Transparency in ingredients (no hidden kryptonite, please)

Now that we’ve covered adrenal supplements, it’s important to remember that even superheroes can have side effects. 

Potential Risks and Side Effects of Adrenal Supplements

Fasten your seatbelts, folks! We’re about to explore the wild world of potential risks and side effects of adrenal supplements.

Possible side effects and interactions

Even superheroes can have off days, and adrenal supplements are no exception. Watch out for these not-so-super side effects:

• Allergic reactions (itchiness, rash, or swelling)
• Digestive issues (upset stomach, gas, or diarrhea)
• Sleep disturbances (because counting sheep should be easy)
• And remember, some adrenal supplements might not play nice with other medications (like a superhero feud that no one wants).

That’s why it’s important to have a journal of your supplements and other factors in your life so that you can easily trace what’s going on wrong in response to your efforts.

When to consult a healthcare professional

Here’s my at-length “cover my butt” section.

If you’re unsure about adding adrenal supplements to your routine, it’s time to communicate with your healthcare provider. They can help you:

• Assess if supplements are right for you (remember: everyone’s different)
• Monitor any side effects (like a trusty sidekick)
• Adjust dosages, if needed (because too much of a good thing can still be bad)

In all seriousness, do this.

You may have other issues going on that need to be considered before adding in chemicals from the internet.

Safe and responsible use of adrenal supplements

Using adrenal supplements safely is like being a superhero with a solid moral compass – it’s all about doing the right thing:

• Start with the lowest dose (you can always level up later)
• Follow the instructions on the label (that’s what they’re there for)
• Keep a symptom journal (to track your progress and any side effects)

As we wrap up our journey through adrenal supplements, it’s important to remember that there’s more to the story. 

Let’s dive into the deeper-rooted issues with adrenal fatigue and the importance of mitochondria – the real powerhouses of our cells (there… I said it)!

Deeper Rooted Issues with Adrenal Fatigue

If you’re experiencing adrenal fatigue, you must know that adrenal fatigue supplements are not the “end all be all.”

You have to get at the root in your mitochondrial!

The Importance of Mitochondria

Mitochondria deserves a standing ovation for their role in keeping our bodies energized and healthy. Let’s give them some love:

• They produce ATP (our body’s energy currency)
• They’re involved in cell signaling, growth, and repair (busy bees!)
• Healthy mitochondria = happy adrenals (and who doesn’t want that?)

Diving Deeper on Mitochondria

Now, we’ve only scratched the surface of this fascinating topic. If you’re curious to learn more about adrenal fatigue, mitochondria, and how they’re connected, then you’re in for a treat!

Watch our FREE masterclass here- https://optimalcircadianhealth.com/class/

Our free masterclass will take you on a thrilling journey into the world of adrenal health and mitochondria. You’ll discover:

• The secrets behind the adrenal fatigue-mitochondria connection
• Powerful strategies to support your adrenal glands and mitochondria

So what are you waiting for? Click the link below to watch our free masterclass and unlock the mysteries of adrenal fatigue and mitochondrial health today!

https://optimalcircadianhealth.com/class/

See you there!

Dylan Petkus, MD 

References:

• Cadegiani, F. A., & Kater, C. E. (2016). Adrenal fatigue does not exist: a systematic review. BMC Endocrine Disorders, 16(1), 48. [link]

• Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian Journal of Psychological Medicine, 34(3), 255-262. [link]

• Lennartsson, A. K., Kushnir, M. M., Bergquist, J., & Jonsdottir, I. H. (2015). DHEA and DHEA-S response to acute psychosocial stress in healthy men and women. Biological Psychology, 104, 1-8. [link]

• Meeusen, R., Duclos, M., Foster, C., Fry, A., Gleeson, M., Nieman, D., … & Urhausen, A. (2007). Prevention, diagnosis, and treatment of the overtraining syndrome: joint consensus statement of the European College of Sport Science and the American College of Sports Medicine. Medicine & Science in Sports & Exercise, 43(1), 186-205. [link]

• Vgontzas, A. N., Zoumakis, E., Bixler, E. O., Lin, H. M., Follett, H., Kales, A., & Chrousos, G. P. (2001). Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. The Journal of Clinical Endocrinology & Metabolism, 86(5), 2449-2453. [link]

• Funder, J. W. (2013). Mineralocorticoid receptor activation and oxidative stress. Hypertension, 62(5), 840-841. [link]

• Kroboth, P. D., Salek, F. S., Pittenger, A. L., Fabian, T. J., & Frye, R. F. (1999). DHEA and DHEA-S: a review. Journal of Clinical Pharmacology, 39(4), 327-348. [link]

• Tsigos, C., & Chrousos, G. P. (2002). Hypothalamic–pituitary–adrenal axis, neuroendocrine factors, and stress. Journal of Psychosomatic Research, 53(4), 865-871. [link]

• Gross, J. J., Fredrickson, B. L., Levenson, R. W., & Miller, G. (2004). The psychophysiology of crying. Psychophysiology, 31(5), 460-468. [link]

• Meeusen, R., Duclos, M., Foster, C., Fry, A., Gleeson, M., Nieman, D., … & Urhausen, A. (2007). Prevention, diagnosis, and treatment of the overtraining syndrome: joint consensus statement of the European College of Sport Science and the American College of Sports Medicine. Medicine & Science in Sports & Exercise, 43(1), 186-205. [link]

• Cuciureanu, M. D., & Vink, R. (2011). Magnesium and stress. In Magnesium in the Central Nervous System (pp. 251-261). University of Adelaide Press. [link]

• Haase, H., & Maret, W. (2003). Intracellular zinc fluctuations modulate protein tyrosine phosphatase activity in insulin/insulin-like growth factor-1 signaling. Experimental Cell Research, 291(2), 289-298. [link]

• Rayman, M. P. (2000). The importance of selenium to human health. The Lancet, 356(9225), 233-241. [link]

• Holick, M. F. (2007). Vitamin D deficiency. The New England Journal of Medicine, 357(3), 266-281. [link]

• Padayatty, S. J., Katz, A., Wang, Y., Eck, P., Kwon, O., Lee, J. H., … & Levine, M. (2003). Vitamin C as an antioxidant: evaluation of its role in disease prevention. Journal of the American College of Nutrition, 22(1), 18-35. [link]

• Rice, M. E. (2004). Ascorbate regulation and its neuroprotective role in the brain. Trends in Neurosciences, 23(5), 209-216. [link]

• Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha root in reducing stress and anxiety in adults. Indian Journal of Psychological Medicine, 34(3), 255-262. [link]

• Olsson, E. M., von Schéele, B., & Panossian, A. G. (2009). A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract SHR-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Medica, 75(02), 105-112. [link]