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Stress and Immunity

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Stress and Immunity

How to Improve Recovery, Fitness and Health Even When Stressed

Introduction - How Stress Ruins Performance and Recovery

As much as we all love to train, and eat right, when you are overcome by a lot of work or life stress you will probably notice your enthusiasm for training suffers and over time this leads to worsening performance, and an increased tendency to gain body fat and lose muscle. That is why improving mental and physical recovery is critical if you want to be the best athlete you can be but the solutions to doing so are not as obvious as just chugging more protein powder. Instead, we need a more innovative approach.

How Cortisol and Stress Interlink with Our Environment

We know that cortisol is our main stress hormone, it not only stimulates our fight or flight response but is critical in enhancing our immune response. How? A sudden peak in cortisol (through stimulation of ADRB2 gene (beta-2 adrenergic receptor) gives us the fight or flight response – our natural and healthy response to threats. If we do not have enough cortisol to “stress” our body, then this process becomes inhibited and you are likely to get eaten by a lion, or fall victim to a viral infection due to a poor immune response.

You can read in detail about what cortisol does here in our previous article but Cortisol and stress are two different entities, although excess stress leads to excess cortisol. Stress encompasses innate, external, physiological and psychological factors. 

The major contributor we have to stress since the Covid-19 pandemic might well be social isolation.

Neuro-immuno-endocrine = Neurotransmitters, immunity, hormones

If you are unable to respond appropriately to a given stress, the resulting disruption of the neuroimmunoendocrine communication leads to a loss of homeostatic balance which can increase the vulnerability to disease.

As you can see here - the green and red lines are moderate to high intensity exercise. After the training, their cortisol remains fairly high. However, compared to the blue line which is LOW INTENSITY, cortisol is reduced.

The link Between Immunity and Chronic Stress

There is a strong causal relationship between chronic stress and a dysfunctional immune system.

Chronic stress leads to inflammation, diminished adrenal function, reduced neurotransmitter output and oxidative stress, all of which put a burden on the immune system. Ever noticed you feel run down when you are anxious or stressed? Well, this is a combination of all those factors combined – the neuroimmunoendocrine system. Now we know what stress is let's review how we can better manage it and improve our health and recovery ability.

Supplements For Stress Support - use code RELIEF at checkout and get 20% off!

An effective way of increasing your resilience to stress is by using adaptogens – these are supplements which help the body resist stress of all kind; physical, chemical or biological. The term adaptogen was first coined by a Russian physician and scientist. It is thrown around a lot wrongly as a term, and there are only a few adaptogens which science purports to exhibit an anxiolytic function: Ashwagandha, rhodiola and resveratrol are the three main ones.

But what is the evidence?

Adaptogens work their effects through modulating neurotransmitters, hormones and cortisol mechanisms; affecting reuptake, synthesis, signalling or even in altering gene expression.

In this article, we are going to look at a few supplements and compounds which have scientific evidence on their effect on mood and stress.

Let’s start with the King of Ayurvedic medicine.

Ashwagandha

One of the main features of Ashwagandha is its calming and anxiolytic effects on the body which is associated with an overall stress-protective activity. Ashwagandha, is an adaptogenic plant with a multitude of experimental studies outlining its bioactive properties. A recent study supplemented individuals with Ashwagandha and measured EEQ frequency in 17 brain regions alongside cognitive performance tests and mood assessment scales. The group who was taking the Ashwagandha improved their concentration and attention on all tests, but most notably their mood was improved (2). A further study concluded the aqueous root extract was beneficial to reduce stress and anxiety especially in those who had issues with sleeping. Sleep is such an important factor in stress. When one is stressed we struggle to sleep, and when we struggle to sleep we are stress. It’s called bidirectional communication (3).

Ashwagandha stacked with a premium rest and relaxation supplement like Revival, one can tackle the aspect of reducing anxiety whilst improving sleep patterns.

Ashwagandha isn’t just the king of Ayurvedic for its anxiolytic effects. Multiple studies have shown root extracts offer immunoprotection through enhanced macrophage colony stimulating factor and reducing expression of TNF-a (an inflammatory cytokine) (4).

Cortisol has been linked to both an increase in oxidative stress and an increase in inflammation within the body. Reducing cortisol by improving our resilience to it can help us to negate the problems associated with high cortisol; one of which is decreased immunity.

Use code RELIEF at Checkout and get 20% off Ashwagandha!

Safranal - An Amazing Herb

Saffron and one of its organic compounds, Safranal, is a common ingredient in South Asian cuisine and noted for its distinctive aroma. Saffron has been shown to improve both sleep quality and to reduce anxiety. We will cover Saffron later as first we look more closely at Safranal.

Safranal’s Effects on Sleep, Anxiety, Mood and Focus

Safranal has been studied for improving sleep with research showing it reduces time to fall asleep as well as improving sleep duration and the critical non-REM sleep where most of us need to spend more time in to improve recovery as well as reduce anxiety (5)[6](7). With sleep disturbances and anxiety highly correlated it is no surprise that if you deal with one you benefit from the other.

Safranal further supports a positive mood through its effects on serotonin and dopamine [8] with research looking as its efficacy for treating depression (9) including one study[10] showing it had comparable or better effects than Prozac (although nobody should ever discontinue a medication they are on without medical approval).

To wrap up its stress supporting benefits, it has also been shown to boost focus and attention which seems odd for a supplement used as a sleep aid but it makes sense when you consider that its actions depend on when you are taking it as well as your dose in much the same way that CBD can be useful for supporting focus and, at a higher dose, support sleep.

Safranal Effects on General Health

Safranal has a wealth of research supporting its ability across a wide range of use cases including:

Anti-inflammatory Effects (11) 
Booasting sexual function in men and women [12][13][14]
Enhanced Cognitive Function (15][16]
Improving PMS symptoms[17](18)
Shows anti-viral properties[19)
Reducing pain[20][21]
Anti-aging[22][23]and immunity benefits[24]
Liver Detoxifying Effects [25][26]

As you can see, Safranal has a huge number of potential health, immune function, and age-busting properties and, believe it or not, this is scratching the surface only with numerous applications for athletes that extent beyond the scope of this piece. Safranal is one of the core ingredients in Hydrapharm's Revival alongside the anxiolytic emoxypine, and various amino acids, minerals and the powerful melatonin analogue 2-Bromomelatonin which work together to promote relaxation and sleep.

You can read a lot more on the science behind safranal at our writeup for Revival.

Use code RELIEF at Checkout and get 20% off Revival!

 

Rhodiola Rosea

Rhodiola rosea is another member of the Ayurvedic medicine as well as being implicated in anxiolytic functions and being called an adaptogen. Some of its other functions include profound anti-inflammatory effects (through regression of COX-1, COX-2 and inhibition of arachidonic acid) (27).

Salidroside, which is a component of rhodiola also shows potential neuroprotective properties in cell culture models by inhibiting genes linked with inflammation such as CD14, CD44, CCR5 (28).

In terms of its adaptogenic properties, rhodiola seems to be highly serotonergic (increases serotonin) and therefore may improve mood. Stress, anxiety and mood variables were measured at baseline and after a 14 day supplementation using rhodiola (29). After the two weeks, there was a significant reduction is self-reported anxiety and stress supporting other similar studies (30).

Use code RELIEF at Checkout and get 20% off Salidroside!

NSI-189

NSI-189 is an experimental compound that is under testing as an antidepressant. It works on two areas on the brain that control the nervous system; the hippocampus and the sub ventricular zone.

Studies have shown mixed outcomes with patients using NSI-189. One study showed that mild improvements in major depressive disorder with a dose dependent manner. The problem with this study was that it had a small sample size, however they did outline a half-life of 17-20 hours for the compound.

This compound has been shown to stimulate neurogenesis in human hippocampus stem cells (in vitro which means in a petri dish). And it is due to this that its “nootropic” ability is used.

It is currently being tested in preclinical trials for: radiation induced cognitive impairment, diabetes related nerve damage, lack of blood flow from stroke diseased brains (31).

NSI-189 has been shown to have a profound effect on mood. This is through its ability to bind to glucocorticoid receptors which results in a decrease of cortisol!

What we can learn about cortisol is that high levels can inhibit our immunity, putting us at risk of catching colds and flu viruses.

NSI-189 can be found in Neurogenesis by Hydrapharm

Use code RELIEF at Checkout and get 20% off Neurogenesis!

Phenibut

Phenibut is a Russian invention which has a long history of use in Russia as an anxiolytic but which has only really gained prominence in the west when it was introduced in the 1990's as a dual action sleep aid and social anxiety solution for bodybuilders who wanted to cut loose but to do so without the detrimental effects on the body or mind associated with drugs such as alcohol or cannabis not to say the destructive properties of harder drugs.

A type of GABA analogue, Phenibut is best used very sparingly once or twice a week, as continued use leads to a huge drop in effectiveness. Dosed at around 500 to 1500mg it can be used to both relax you and to help you sleep. 

Phenibut can be found in Phenibut by Fusion Supplements.

Use code RELIEF at Checkout and get 20% off Phenibut!

 

Conclusion

Although it is not fully clear what all the exact mechanisms are as to how different nootropics or adaptogens combat stress, it seems that a key part is attenuating the negative effects of a heightened sympathetic nervous system as well as improving neurotransmitter levels and functions including dopamine, and serotonin to name just two.

When we encounter periods of heavy stress, review the science behind the ingredients we have covered and we also recommend reading the references below for an even more detailed look at each one. By using such products on an as needed basis and also managing your environmental stressors better whether that is via a healthier diet, improving sleeping habits, or adopting meditation, you need not struggle quite as much when stress enters your life and hopefully by adapting these kinds of strategies, your body and mind are better supported over the long haul and you need not lose a lot of your fitness gains in the process.

 

References

1. http://ijbsm.zbmu.ac.ir/FullHtml/IJBSM-1-20160701032654

2. https://www.ncbi.nlm.nih.gov/pubmed/32183355

3. https://www.ncbi.nlm.nih.gov/pubmed/32021735

4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438434/

5. Safranal enhances non-rapid eye movement sleep in pentobarbital-treated mice. CNS Neurosci Ther.Liu Z, Xu XH, Liu TY, Hong ZY, Urade Y, Huang ZL, et al

6. Anxiolytic and hypnotic effect of Crocus sativus aqueous extract and its constituents, crocin and safranal, in mice.Hosseinzadeh H1, Noraei NB.

7. Effects of Saffron on Cognition, Anxiety, and Depression in Patients Undergoing Coronary Artery Bypass Grafting: A Randomized Double-Blind Placebo-Controlled Trial.Moazen-Zadeh E1, Abbasi SH2, Safi-Aghdam H1, Shahmansouri N2, Arjmandi-Beglar A2, Hajhosseinn Talasaz A2, Salehiomran A2, Forghani S3, Akhondzadeh S1.

8. Saffron (Crocus sativus L.): As an Antidepressant Mohammad J. Siddiqui, Mohammed S. M. Saleh, Siti N. B. Binti Basharuddin, Siti H. Binti Zamri, Mohd H. bin Mohd Najib, Muhammad Z. bin Che Ibrahim, Nur A. binti Mohd Noor, Hanin N. Binti Mazha, Norazian Mohd Hassan, and Alfi Khatib

9. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. Heather Ann Hausenblas, Ph.D., Debbie Saha, B.S., Pamela Jean Dubyak, M.S., and Stephen Douglas Anton, Ph.D.

10. Comparison of Saffron versus Fluoxetine in Treatment of Mild to Moderate Postpartum Depression: A Double-Blind, Randomized Clinical Trial. Kashani L, Eslatmanesh S, Saedi N, Niroomand N, Ebrahimi M, Hosseinian M, Foroughifar T, Salimi S, Akhondzadeh S.

11. Antinociceptive and anti-inflammatory effects of Crocus sativus L stigma and petal extracts in mice. BMC Pharmacol. 2002;15:2–7.

12. The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats. Phytomedicine . 2008;15:491–495.Hosseinzadeh H, Ziaee T, Sadeghi A.

13. Evaluation of Crocus sativus L (saffron) on male erectile dysfunction. Shamsa A, Hosseinzadeh H, Molaei M, Shakeri MT, Rajabi O

14. Saffron for treatment of fluoxetine-induced sexual dysfunction in women: randomized double-blind placebo-controlled study. Kashani L, Raisi F, Saroukhani S, Sohrabi H, Modabbernia A, Nasehi AA, Jamshidi A, Ashrafi M, Mansouri P, Ghaeli P, Akhondzadeh S.

15. Effects of saffron (Crocus sativus L) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytother Res . 2012;26:381–386. Hosseinzadeh H, Sadeghnia HR, Ghaeni FA, Motamedshariaty VS, Mohajeri SA.

16. Effects of Crocus sativus stigma extract and its constituents, crocin and safranal, on intact memory and scopolamine induced learning deficits in rats performing the Morris water maze task. J Med Plants H Hosseinzadeh, T Ziaei

17. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. Agha-Hosseini M1, Kashani L, Aleyaseen A, Ghoreishi A, Rahmanpour H, Zarrinara AR, Akhondzadeh S.

18. The effect of an Iranian herbal drug on primary dysmenorrhea: a clinical controlled trial. Nahid K, Fariborz M, Ataolah G, Solokian S.

19.  Antiviral Effects of Saffron and its Major Ingredients. Soleymani S, Zabihollahi R, Shahbazi S, Bolhassani A.

20. An overview on saffron, phytochemicals, and medicinal properties. Ahmad Reza Gohari, Soodabeh Saeidnia, and Mahdie Kourepaz Mahmoodabadi

21. Effects of Saffron (Crocus sativus L.) Stigma Extract and its Active Constituent Crocin on Neuropathic Pain Responses in a Rat Model of Chronic Constriction Injury. Hossein Ali Safakhah, Tahereh Taghavi, Ali Rashidy-Pour, Abbas Ali Vafaei, Mina Sokhanvar, Narges Mohebbi, and Mostafa Rezaei-Tavirani

22. Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial.Akhondzadeh S, Sabet MS, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi SSh, Yousefi MH, Alimardani R, Jamshidi A, Zare F, Moradi A.

23. Effects of Crocus sativus Stigma Extract and its Constituents, Crocin and Safranal, on Intact Memory and Scopolamine-Induced Learning Deficits in Rats Performing the Morris Water Maze Task. H Hosseinzadeh, T Ziaei

24. Immunomodulatory effects of saffron: a randomized double-blind placebo-controlled clinical trial. Kianbakht S, Ghazavi A.

25. Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats.Arash Omidi, Narges Riahinia, Mohammad Bagher Montazer Torbati, and Mohammad-Ali Behdani

26. Saffron as an antidote or a protective agent against natural or chemical toxicities. Bibi Marjan Razavi and Hossein Hosseinzadeh

27.5. Xiong, Y., and Gao, L. L. (2017). Salidroside affects spatial memory,NF-κB and COX-2 expressions in vascular dementia rats. Chin. Arch. Tradi. Chin. Med. 35, 402–404. doi: 10.13193/j.issn.1673-7717.2017.02.040

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31. https://www.spandidos-publications.com/10.3892/mmr.2015.3698

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34. Chamomile (Matricaria recutita) may provide antidepressant activity in anxious, depressed humans: an exploratory study. Amsterdam JD, Shults J, Soeller I, Mao JJ, Rockwell K, Newberg AB. Altern Ther Health Med. 2012 Sep-Oct; 18(5):44-9.

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