Thursday, November 9, 2017

16 Little Known Plants + Phytocompounds to Control(!) Your Cortisol Levels | Plus: A Dozen Better-Known Alternatives

Don't forget: Cortisol is no stressor, it's released to help us cope w/ stress.
While I have repeatedly emphasized that the notion of cortisol as the "muscle-catabolic stress hormone" you have to "keep as low as possible" is fundamentally flawed, there are reasons why you may want to control your cortisol levels within what would be considered the circadian normal zone, i.e. high(er) levels of cortisol that get you going upon waking, lower levels of cortisol in the PM and at night to facilitate optimal glucose control, avoid HPTA suppression (=keep normal thyroid, GH, and testosterone/estrogen levels), allow for healthy and recuperative sleep and so on and so forth.

If you are physically healthy and not overweight/obese, you are probably able to achieve this goal if you have the following (health) habits: (1) getting enough sleep (6-8h), (2) adhering to fundamental rules of sleep hygiene (same time, same routine, no blue light exposure before and during the sleep phase, etc.), (3) not starving yourself/depriving yourself of carbs while trying to get away w/ most energy from protein, not fat, (4) controlling your workout volume and using periodization strategies to benefit from temporary overreaching while avoiding chronic overtraining, (5) meditation and other techniques to reduce and/or cope with stress (learn more in "Take control of your cortisol levels").
Chronically elevated glucocorticoids can occur in the early phase of overtraining:

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Unfortunately, it is not always possible to control/reduce your stress exposure solely by behavioral means. In those situations, medicinal plants that can modulate your hormonal response to stress can come handy. A group of less-known medicinal plants and herbal products has recently been reviewed by scientists from the Shahrekord University of Medical Sciences in Iran (Solati 2017).

For their recently published review, Solati, Heidar-Soureshjani, and Pocock considered all papers describing herbal/medicinal plant treatments that will ameliorate or normalize the production of corticotropinreleasing hormone (CRH), adrenocorticotropic hormone (ADH), or cortisol (CORT), directly.
Of the initial 884 studies that turned out in response to the scientists' keyword search, the authors excluded 738 because they were, upon closer scrutiny, out of date, had an insufficient scope or were duplicates. Of the remaining 146 studies 30 were excluded, because there was no English-language full text. Another 94 did not measure any of the three target hormones and were likewise eliminated. Eventually, the authors were thus left with only 19 studies they grouped into studies investigating the effects of medicinal plants (meaning you would have to ingest a decoction, brew a tea (water extraction) or simply eat parts of the plant) and phytocompounds (meaning you would have to buy a supplement or extract certain substances from a plant yourself).
Table 1 & 2: Plants (left) and phytocompounds w/ stress modulating effects
Complex blends (proprietary or not) such as Si Ni Tang, a Chinese herbal combination consisting of Glycyrrhiza uralensis, Zingiber officinale, and Aconitum carmichaeli, a traditional mix of Magnolia ofifcinalis and Phellodendron amurense, or Zhi-Zi-Hou-Po, which consists of Gardenia jasminoides Ellis fruit, Citrus aurantium L. fruit and Magnolia offcinalis Rehd. et Wils. bark were not included in the tabular overviews, but still showed promising effects in experimental investigations:
  • Figure 1: Effects of Andrographis paniculata extract (AP), andrographolide (Andro), and Withania somnifera extract (WS) on plasma corticosterone level of chronically stressed rats. Values are Mean ± SEM (n = 6), *p < 0.05 versus normal control; ¥p < 0.05 versus stressed control (Thakur 2014). Note: The classic adaptogen WS performs best.
    Si Ni Tang (Glycyrhhiza uralensis, Zigiber officinale, and Aconitum carmichaeli) modulated increase in corticosterone and therefore helped relieve stress in a rodent model of unpredictable (≠everyday) stressors (41) and modulated both corticosterone and ACTH while increasing the mRNA expression of hippocampal glucocorticoid receptors in another study (Wei 2016).
  • Magnolia officinalis and Phellodendron amurense in stressed human beings yielded a significant decrease in oral cortisol levels over 4 weeks of continuous treatment (Talbott 2013).
  • Zhi-Zi-Hou-Po, consisting of Gardenia jasminoides Ellis fruit, Citrus aurantium L. fruit and Magnolia officinalis Rehd. et Wils. bark, caused normalization of ACTH and CORT levels in a rat model of unpredictable chronic mild stress (Xing 2015).
In conjunction with the 14 items from Table 1 + 2 that's a total of 17 different "herbals" (in the widest sense) you can use as a complement to behavioral modifications to keep your cortisol levels within their normal circadian patters (high in the AM, a steady decline with intermediate increases before/right after meals).

One simply has to repeat, however: goal must not be to annihilate cortisol!

Even if you haven't read my previous articles about the performance enhancing, inflammation controlling, recovery facilitating and even weight loss and glycemic benefits of normal levels of cortisol, a closer look at the effect summaries in Table 1 + 2 teaches us that…
  • Figure 2: Icariin is better known for its virility effects, but it's also a potent stress-reducer as a 2010 rodent study (chronic stress vs. control) indicates; sign. reductions in both corticotropin-releasing factor (CRF) and cortisol were observed in response to the HED of 5 and 10 mg/kg Icariin daily (Pan 2010).
    Valeriana jatamansi will also reduce the level of the "happy neurotransmitter" 3-endorphin,
  • Shyusan could reduce the glucocorticoid activity to a degree that will significantly increase your risk of hypoglycemia – especially on low-carb + high protein diets,
  • YZ-50 will impair the natural auto-regulatory mechanisms of the HPA, or
  • Icariin will also reduce the number of serotonin receptors in the hippocampus and frontal cortex and will thus mess w/ your brain chemistry or rather your brains response to a given level of neurotransmitters
Both, the initially mentioned a too drastic reduction of the levels of cortisol and its controlling hormones CRH and ADH, as well as "corollary damage" in form of changes in neurotransmitter levels are something you must at least keep an eye on, when you're using any of the herbals from Solati et al.'s list to modulate, control, or (if necessary) reduce your cortisol levels.

What other, better-known cortisol controlling agents are there? 

While this review focuses on less well-known compounds. From previous articles or other web sources you will yet know that there is a dozen of better-known alternatives:

Starting with vitamin C that can reduce the cortisol release in response to running an ultramarathon if it's taken at a high dosage of 1,500mg/d for 7 days before the marathon (do not use chronically or you may impair your gains). An ameliorative effect on the exercise-induced increase in cortisol was also observed in 9 healthy male subjects in response to 15 mmol magnesium-L-aspartate-hydrochloride (that's 365 mg/d) taken daily for 14 days. What's odd is that a newer study by Cinar, et al. (2008) in which 10 mg/kg of magnesium sulfate were supplemented, the opposing effects, i.e. an increase in the cortisol response to exhausting exercise was observed. An effect you may remember from another common supplement: caffeine, which will also raise your cortisol levels and your cortisol response to exercise (Lovallo 2006; Slivka 2008).

Amino acid supplements (BCAA 140mg/kg + arginine 100mg/kg + ornithine 80 mg/kg) have also been shown to have complex effects on the cortisol response to exercise, with lower baseline and post-exercise cortisol levels in response to 320mg/kg body weight (vs. placebo) consumed 60 minutes before a standardized workout, but a significantly more pronounced increase of cortisol from pre- to post-exercise (in general, that's good news: you want a large amplitude in the ups and downs of your cortisol levels) - an effect that was not observed in response to a protein supplement in Fry, et al. 1993 or a protein + carbohydrate mix in Williams et al. (2002).
Figure 2:  Effects of whey (WPI) vs. soy (SPI) PWO supplement on changes in cortisol (nmol·L−1). *Significantly different from PRE value ( p ≤ 0.05), †Significantly ( p ≤ 0.05) different from WPI treatment (Kraemer 2013).
Unlike soy protein, the provision of fast digesting whey protein (which also contains several bioactive peptides) has a small, but measurable effect on the exercise-induced post-workout cortisol spikes (Kraemer 2013).

Another better-known group of cortisol control agents are the so-called adaptogens

Adaptogens are (in herbal medicine) natural substances considered to help the body adapt to stress. Almost all of them will also affect the levels of cortisol, with ginseng, holy basil, ashwaghanda (Withania somnifera, see Figure 1, WS), astragalus, rhodiola rosea and cordyceps having cortisol-reducing, and licorice root and caffeine having cortisol increasing/promoting effects.
Figure 4: Cortisol concentrations in saliva on 4 test days. PC = placebo maintenance followed by 3 × 250-mg caffeine. C300 = 300 mg/d of caffeine at home followed by caffeine challenge on the test day. C600 = 600 mg/d at home followed by caffeine challenge on the test day. PP = placebo at home and placebo on test day. Base 1, Base 2, Base 3 = saliva samples taken immediately before taking a caffeine or pla capsule. PostC = samples taken 1h postdrug. Stress and Recov = samples taken at the end of a 30-min behavioral stress period or after 30 min of recovery (Lovallo 2005).
Especially with respect to caffeine, you should remember, though, that its chronic consumption will significantly reduce its efficacy - if that's a good or a bad thing, obviously depends on whether your goal is to ameliorate or boost your cortisol levels.

Patented substances and proprietary blends

The DHEA-metabolite 7-keto, but not DHEA itself, can also sign. reduce your cortisol levels by inhibiting the conversion (/activation) of cortisone to cortisol.

Figure 5: 7-Keto inhibits the conversion of inactive cortisone to active cortisol.
The studies showing beneficial downstream effects on metabolism or body composition were however all done in subjects w/ overweight/obesity - there's yet no doubt that the general effect on cortisol production will occur in lean(er) individuals, as well.

Next to the proprietary DHEA-metabolite, there's also Cortitrol a proprietary blend of Magnolia (Magnolia officinalis) bark Extract (9.5 mg), Epimedium (Epimedium koreanum, Extract 100 mg which contains Icariin herb ), L-Theanine (TheaPure, 67.5 mg), Plant Sterols (with Beta Sitosterol 55 mg), and Phosphatidylserine (8.3 mg), all of which have some research to back up their effects on cortisol, individually. It is thus not totally surprising that sponsored trials report significant reductions in serum cortisol responses to physical stress (Kraemer 2005).
Take Control of Your Cortisol Levels - Use These 5x Stress-Modulating Diet, Lifestyle & Supplementation Rules Wisely | more
Bottom line: You can find a brief overview of the herbals mentioned in the review at hand in Table 1 + 2. Keep in mind, though, you do not want to annihilate your cortisol levels. Having chronically low levels of cortisol can trigger hypoglycemic episodes (often w/ a racing heart and/or high blood pressure, because an increase in catecholamines needs to compensate the lack of cortisol), general fatigue, exuberant inflammation, joint pain, allergies, sleeping problems, etc.

Ideally, you'd get a 4x/d salivary cortisol baseline reading to know if your fat belly is in fact caused by high cortisol levels, not simply by eating too much, before you embark on any (higher dose) supplement regimen for cortisol control.

Plus: If you stumble across one of the referenced write-ups on commercially available cortisol blockers, make sure to check if the studies that are quoted are even relevant for you. 7-Keto, for example, has decently convincing results in the short run in obese/heavily inflamed individuals. Neither its long-term safety, nor its efficacy in healthy, lean, athletic folks has been studied sufficiently, though | Comment!
  • Cinar, Vedat, et al. "Adrenocorticotropic hormone and cortisol levels in athletes and sedentary subjects at rest and exhaustion: effects of magnesium supplementation." Biological trace element research 121.3 (2008): 215-220.
  • Fry, Andrew C., et al. "Endocrine and performance responses to high volume training and amino acid supplementation in elite junior weightlifters." International journal of sport nutrition 3.3 (1993): 306-322.
  • Golf, S. W., et al. "Plasma aldosterone, cortisol and electrolyte concentrations in physical exercise after magnesium supplementation." Clinical Chemistry and Laboratory Medicine 22.11 (1984): 717-722.
  • Kraemer, William J., et al. "Cortitrol supplementation reduces serum cortisol responses to physical stress." Metabolism 54.5 (2005): 657-668.
  • Lovallo, William R., et al. "Caffeine stimulation of cortisol secretion across the waking hours in relation to caffeine intake levels." Psychosomatic medicine 67.5 (2005): 734.
  • Lovallo, William R., et al. "Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women." Pharmacology Biochemistry and Behavior 83.3 (2006): 441-447.
  • Pan, Ying, et al. "Icariin attenuates chronic mild stress-induced dysregulation of the LHPA stress circuit in rats." Psychoneuroendocrinology 35.2 (2010): 272-283.
  • Peters, E. M., et al. "Vitamin C supplementation attenuates the increases in circulating cortisol, adrenaline and anti-inflammatory polypeptides following ultramarathon running." International journal of sports medicine 22.07 (2001): 537-543.
  • Smriga, Miro, et al. "Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans." Biomedical Research 28.2 (2007): 85-90.
  • Solati K, Heidari-Soureshjani S, Pocock L.. Effects and mechanisms of medicinal plants on stress hormone (cortisol): A systematic review. World Family Medicine. 2017; 15(9):117-123. DOI: 10.5742/MEWFM.2017.93115.
  • Talbott SM, Talbott JA, Pugh M. Effect of Magnolia offcinalis and Phellodendron amurense (Relora (R)) on cortisol and psychological mood state in moderately stressed subjects. J Int Soc Sport Nutr. 2013;10.
  • Wei SS, Yang HJ, Huang JW, Lu XP, Peng LF, Wang QG. Traditional herbal formula Sini Powder extract produces antidepressant-like effects through stress-related mechanisms in rats. Chinese journal of natural medicines. 2016;14(8):590-8.
  • Williams, Alun G., et al. "Effects of resistance exercise volume and nutritional supplementation on anabolic and catabolic hormones." European journal of applied physiology 86.4 (2002): 315-321.
  • Xing H, Zhang K, Zhang R, Shi H, Bi K, Chen X. Antidepressant-like effect of the water extract of the fixed  combination of Gardenia jasminoides, Citrus aurantium and Magnolia offcinalis in a rat model of chronic unpredictable mild stress. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2015;22(13):1178-85.