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Cordyceps militaris - Rat Study Finds Unexpected Nephrotoxicity

cordyceps

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#1 Mr. Olive Oil

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Posted 15 January 2018 - 01:27 AM


I am interested in hearing thoughts on this study... whether it is faulty or worth making a mental note about.

Human dosages after I converted the lowest 1g/kg for rats = 162 mg/kg. So 90 kg human = 14.5 grams per day.

 

I take around one gram per day and I think most people are in that range as well.

https://www.hindawi....am/2013/786528/

 

Unexpected Nephrotoxicity in Male Ablactated Rats Induced by Cordyceps militaris: The Involvement of Oxidative Changes

 

Herein, we carried out the 28-day repeated toxicity test in male and female ablactated rats (three weeks old) given C. militaris powder orally at 0 (control), 1, 2, and 3 g/kg per day. Noticeable increments of serum aspartate and alanine aminotransferase (ALT and AST) levels were observed for both sexes, suggestive of weak hepatic toxicity. Nephrotoxicity characterized by tubular epithelium degeneration and necrosis was observed at the high dose, and the male rats were more susceptible to renal toxicity than female rats. In addition, the genes and protein expressions of novel markers of kidney toxicity, such as kidney injury molecule-1 (KIM-1) were enlarged in the renal cortex and the urine. Moreover, C. militaris treatment significantly decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. However, the ratio of glutathione oxidized form (GSSG)/glutathione reduced form (GSH) was increased by C. militaris treatment. We conclude that dietary contamination with C. militaris may have renal toxicity potentials, at least in part by causing oxidative damage to the kidney.

 

KIM-1 Expression

CCM treatment caused significant up-regulation of kIM-1 gene and protein expression in the renal cortex and the urine (Figure 4). In details, kIM-1 mRNA levels in male rats were increased of 4-, 20-, or 61-fold versus control by 1, 2, and 3 g/kg treatment, respectively (Figure 4(a)), whereas kIM-1 mRNA increment in female rats was only observed at the high dose (16-fold versus control). The protein level of kIM-1 also amplified significantly in male rats (35-fold) (Figure 4(b)). The same tendency, although not statistically significant, was noted in urine kIM-1 expression in male rats (Figure 4©). Nevertheless, no significant difference of kIM-1 protein level was observed in both renal cortex and urine for the female rats.

 

Antioxidant Enzyme Activities

Antioxidant enzyme activities (SOD, CAT, GR, GPx, and GST) and the oxidative stress maker GSSG/GSH ratio in renal cortex of ablactated rats given CCM are summarized in Table 7. For male rats, a significant reduction in SOD, CAT and GPx activities in 3 g/kg group was observed compared with the control group. The same tendency, although not statistically significant, was noted in GR activity. As expected, GSSG/GSH ratio was enhanced in CCM-treated rats. No changes were observed in the GST activity. For female rats, only SOD activity exhibited a decline and GSSG/GSH ratio showed an apparent increase, and the differences reached the level of statistical significance.


Edited by highlightfocus, 15 January 2018 - 01:31 AM.

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#2 ta5

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Posted 15 January 2018 - 03:18 AM

I'm interested in this as well since I just bought some to try. This study references your study:

 

Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions

Takakura K, Ito S, Sonoda J, Tabata K, Shiozaki M, Nagai K, Shibata M, Koike M, Uchiyama Y, Gotow T.

Heliyon. 2017 Nov 24;3(11):e00462.

 

"First, we determined the daily amount of CM that should be administered to the Dahl rats. Since a high dose of CM (3 g/kg (body weight)/day) was considered harmful to the kidneys of rats (Zhou and Yao, 2013), we selected an amount that would approximate such a dose to more clearly define the influence of CM and either the benefit or harm to these hypertensive rats that had been fed a high-salt diet"

 

Then, I didn't see that they found any kidney damage. But, maybe I missed it...


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#3 Mr. Olive Oil

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Posted 16 January 2018 - 07:34 AM

I'm interested in this as well since I just bought some to try. This study references your study:

 

Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions

Takakura K, Ito S, Sonoda J, Tabata K, Shiozaki M, Nagai K, Shibata M, Koike M, Uchiyama Y, Gotow T.

Heliyon. 2017 Nov 24;3(11):e00462.

 

"First, we determined the daily amount of CM that should be administered to the Dahl rats. Since a high dose of CM (3 g/kg (body weight)/day) was considered harmful to the kidneys of rats (Zhou and Yao, 2013), we selected an amount that would approximate such a dose to more clearly define the influence of CM and either the benefit or harm to these hypertensive rats that had been fed a high-salt diet"

 

Then, I didn't see that they found any kidney damage. But, maybe I missed it...

 

Good find ta5, thank you for posting. Hopefully more people can jump in and critique the hell out of these studies.

 

In study you posted, the section I saw related to kidneys was:

 

3.2.3. Glomeruli and renal tubules in the kidney

"The kidney is susceptible to hypertension and injury in Dahl rats (Khan et al., 2013). Light microscopy showed the glomerular blood capillaries had collapsed with lumens that had almost disappeared and Bowman’s urinary spaces that were cramped in the control rats, but the capillary lumens and urinary spaces were clearly detectable in the CM-treated rats (Fig. 6). The renal and collecting tubules had similar profiles in both groups, but the lumens tended to contain more amorphous substance in the control rats (Fig. 6).

Electron microscopy showed podocytes with foot processes that were irregular in width and sometimes effaced in the control rats (Fig. 7). Mitochondria in the podocytes were scanty in both rats, and frequently swollen in the control rats. In the control rats, the glomerular blood capillaries were frequently congested with erythrocytes and leukocytes (Fig. 7), as shown by the collapsed capillary images shown in light microscopy. The glomerular structures looked normal in the CM-treated rats. In the renal tubules, mitochondria were more abundant in the epithelial cells than in the podocytes, and they showed a slightly denser cytoplasmic matrix with enhanced pinocytosis and irregularly aligned microvilli in the control rats. These profiles were almost normal in the CM-treated rats (Fig. 7). The lumens of the renal tubules in the control rats were occupied with proteinaceous materials more frequently compared with the CM-treated rats (Fig. 7). It was clear that CM improved the hypertension-induced podocyte injury that causes proteinuria and results in a possible dysfunction of the renal tubules."

 

It seems to have some beneficial effects in the above section. As you said, they do acknowledge the other study and mimic the same high dosing scheme yet they later don't seem to be looking for carcinogenic activity. The control rats were already in a hypertensive state, so cordyceps seem to mitigate some of the issues.

 

"Microscopically, CNS neurons, cardiomyocytes, glomerular podocytes, renal epithelial cells, and hepatocytes all were improved. However, immunoblot and immunohistochemical analysis showed that the expressions of mitochondria-related proteins, ATP synthase β subunit, SIRT3 and SOD2, and autophagy-related proteins, LC3-II/LC3-I ratio and cathepsin D all were reduced significantly in the CNS neurons, but increased significantly in the cells of the other three organs, although p62 was decreased in its expression in all the organs tested. Activity of Akt and mTOR was enhanced but that of AMPK was reduced in the CNS, while such kinase activity was completely the opposite in the other organs."

 

Very complex results here depending on location. A lot of opposite activities occurring.

Seems to show a SOD decrease in neurons but not in kidneys. The first study showed a decrease in kidney SOD.

 

 


Edited by Mr. Olive Oil, 16 January 2018 - 07:37 AM.


#4 Mr. Olive Oil

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Posted 16 January 2018 - 11:36 AM

A follow up to my last post regarding SOD2. This is going off-topic from the kidney concerns but...

By chance I stumbled on a post by Joe Cohen just now (I was researching MitoQ on Lostfalco's giant thread).

 

It seems the decreased expression of SOD2 in the neurons by Cordyceps in the above study might actually be a good thing. Perhaps it is increasing the MnSOD enzyme that reduces SOD2?

 

Link to his full post:

http://www.longecity...ndpost&p=718759

 

Quote from post:

 

"MitoQ is also quite useful, but you'd want to check if you've got the SOD2 mutation like I do and a very large percentage of my brain fog clients.  Brain fog is caused by superoxide in the hypothalamus and perhaps more specifically in the mitochondria.  That mutation means you break down superoxide signifcantly less well.  MitoQ breaks down superoxide in the mitochondria.  I need to take 20mg for it to have a very noticeable effect. "

 

"The SOD2 mutation causes a 33% decrease of the enzyme (MnSOD) that breaks down superoxide in the mitochondria.  Superoxide production is the most significant cause of brain fog.

In 2014, two studies found that the level of genes expression of SOD2 (MnSOD) is strongly correlated with cognitive performance. (RR2)

The main SOD2 gene (rs4880(C;C)) is extremely common in my brain fog clientele and there’s a lot of scientific research on it.

Three other SOD2 genes are also heavily overrepresented in my clientele and include: rs2758331 (AA), rs2758339 (CC), rs10370 (AA).  Although little science has been done on these and the most important gene is rs4880(C;C)."

http://selfhacked.co...e-of-brain-fog/


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#5 Galaxyshock

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Posted 16 January 2018 - 02:02 PM

Does this also apply to Cordyceps Sinensis?



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#6 EFTANG

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Posted 12 February 2018 - 03:51 PM

What I think is wrong about this study and the majority of studies dealing with herbals and botanicals is that they do not map the active compounds in the herb.

 

Overlooking that one Cordyceps fruiting body might be completely different in many aspects when compared against another, depending on strain, cultivation method, environmental conditions, storage etc...  many many variables to take into account and yet the herb/mushroom is treated as if it is some standardised product.

 

I think that is a fundamental flaw making these studies unreliable.  For instance, I remember reading somewhere that Cordyceps militaris is often grown in plastic containers but sometimes the plastic (depending on the type) was affected by the mushroom or parts of it, causing decomposition and absorption of plastic particles. Things like that can influence research results enormously.


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