Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?

[Lokzo]

Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?​

Amarnath Sen
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Abstract​

Different mechanisms forwarded to understand anosmia and ageusia in coronavirus patients are not adequate to explain reversible anosmia and ageusia, which are resolved quickly. In addition, the reason behind the impaired chemesthetic sensations in some coronavirus patients remains unknown. In the present paper it is proposed that SARS-CoV-2 patients suffer from depletion of tryptophan, as ACE2, a key element in the process of absorption of tryptophan from the food, is significantly reduced in the patients as coronavirus uses ACE2 as the receptor to enter the host cells. The tryptophan depletion leads to a deficit of serotonin (5-HT) in SARS-COV-2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency can explain anosmia, ageusia and dysfunctional chemesthesis in COVID-19, given the fact that 5-HT is an important neuromodulator in the olfactory neurons, taste receptor cells and transient receptor potential channels (TRP channels) involved in chemesthesis. In addition, 5-HT deficiency worsens silent hypoxemia and depresses hypoxic pulmonary vasoconstriction leading to increased severity of the disease. Also, the levels of anti-inflammatory melatonin (synthesized from 5-HT) and nicotinamide adenine dinucleotide (NAD+, produced from niacin whose precursor is the tryptophan) might decrease in coronavirus patients resulting in the aggravation of the disease. Interestingly, selective serotonin reuptake inhibitors (SSRIs) may not be of much help in correcting the 5-HT deficiency in COVID-19 patients, as their efficacy goes down significantly when there is depletion of tryptophan in the system. Hence, tryptophan supplementation may herald a radical change in the treatment of COVID-19 and accordingly, clinical trials (therapeutic / prophylactic) should be conducted on coronavirus patients to find out how tryptophan supplementation (oral or parenteral, the latter in severe cases where there is hardly any absorption of tryptophan from the food) helps in curing, relieving or preventing the olfactory, gustatory and chemesthetic dysfunctions and in lessening the severity of the disease.

Full article here: Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?

 

[RealNeat]

Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?​

Amarnath Sen
Author information Article notes Copyright and License information Disclaimer
This article has been cited by other articles in PMC.

Go to:

Abstract​

Different mechanisms forwarded to understand anosmia and ageusia in coronavirus patients are not adequate to explain reversible anosmia and ageusia, which are resolved quickly. In addition, the reason behind the impaired chemesthetic sensations in some coronavirus patients remains unknown. In the present paper it is proposed that SARS-CoV-2 patients suffer from depletion of tryptophan, as ACE2, a key element in the process of absorption of tryptophan from the food, is significantly reduced in the patients as coronavirus uses ACE2 as the receptor to enter the host cells. The tryptophan depletion leads to a deficit of serotonin (5-HT) in SARS-COV-2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency can explain anosmia, ageusia and dysfunctional chemesthesis in COVID-19, given the fact that 5-HT is an important neuromodulator in the olfactory neurons, taste receptor cells and transient receptor potential channels (TRP channels) involved in chemesthesis. In addition, 5-HT deficiency worsens silent hypoxemia and depresses hypoxic pulmonary vasoconstriction leading to increased severity of the disease. Also, the levels of anti-inflammatory melatonin (synthesized from 5-HT) and nicotinamide adenine dinucleotide (NAD+, produced from niacin whose precursor is the tryptophan) might decrease in coronavirus patients resulting in the aggravation of the disease. Interestingly, selective serotonin reuptake inhibitors (SSRIs) may not be of much help in correcting the 5-HT deficiency in COVID-19 patients, as their efficacy goes down significantly when there is depletion of tryptophan in the system. Hence, tryptophan supplementation may herald a radical change in the treatment of COVID-19 and accordingly, clinical trials (therapeutic / prophylactic) should be conducted on coronavirus patients to find out how tryptophan supplementation (oral or parenteral, the latter in severe cases where there is hardly any absorption of tryptophan from the food) helps in curing, relieving or preventing the olfactory, gustatory and chemesthetic dysfunctions and in lessening the severity of the disease.

Full article here: Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?

I didn't know this, " ...given the fact that 5-HT is an important neuromodulator in the olfactory neurons, taste receptor cells and transient receptor potential channels (TRP channels) involved in chemesthesis."

But it seems to be a different perspective than that of Ray, as he has recommended people take serotonin antagonists like cinanserin. It (cinanserin) also shows efficacy in previous so called coronavirus infections.

Curious how the supposed/ proposed mechanisms of harm could be such polar opposites.

 

[Gustav3Y]

There was a study showing people with high 5-HT and 5 HIAA (5-HT metabolite) had worse COVID symptoms than those with lower of both, someone posted it a long time ago.
How is that explained then?

 

[Hans]

The reason for this is because tryptophan is not being absorbed due to a reduction in the transporter. The unabsorbed tryptophan is then used by bacteria to create harmful metabolites. The way to fix this is not to give more tryptophan or use SSRIs, but rather resolve the dysbiosis caused by COVID in the first place, which should then upregulate the tryptophan transporter.

 

[Perry Staltic]

But it seems to be a different perspective than that of Ray, as he has recommended people take serotonin antagonists like cinanserin. It (cinanserin) also shows efficacy in previous so called coronavirus infections.

I think 5HT antagonism might make sense in a dysfunctional system, but doing so in a healthy system makes no sense.

 

[Stifler]

So is there such thing as serotonin deficiency ? From what I've read it doesn't seem like RP would believe in such a thing, is there a baseline level of serotonin required to function ?

 

[Gustav3Y]

One thing is that pro-serotonin studies exist out there, so if you want you can unleash the gates of pro-serotonin.
I am not making a statement, just saying that one should be so surprised.

 

[Gustav3Y]

Serotonin is elevated in COVID-19-associated diarrhoea

Serotonin is elevated in COVID-19-associated diarrhoea | Gut

 

[Gustav3Y]

So now everyone will jump on SSRIs.
Like I have said you can find extremely positive studies with regard to Serotonin, I just hope people realize that this is nothing new at all, it was just a matter of time their association with COVID was to come.




"Apparently, an administration of SSRIs is expected to boost the 5-HT level and provide much relief to the patients. However, no clinical study has been done with a view to correcting the 5-HT deficiency of coronavirus patients as the possibility of such 5-HT deficiency has not been considered earlier. Nevertheless, on the basis of the existing knowledge that some SSRIs have anti-inflammatory, antiviral, immunoregulatory and neuroprotective properties, a few studies [114], [115], [116], [117], [118] have been carried out to explore the effect of SSRIs on the coronavirus patients, where SSRIs like fluvoxamine, fluoxetine and escitalopram have been found to somewhat decrease the severity of COVID-19. This observation is in line with the present hypothesis, though, as anticipated from the hypothesis, a significant improvement is lacking."

 

[Mauritio]

fluoxetine

It is a 5HT2c antagonist which might explain some of the benefits.

Well, if you just Google "SSRI allopregnanolone" you will get plenty of studies. It is a well-known link and there have been proposals to change the designation of SSRI drugs into something like "selective steroid synthesis enhancers" to reflect their focus on neurosteroids. Also, many of the SSRI are actually selective antagonists on 5-HT2C so that explains some of their effects as well. It is unfortunate that there drugs are systemically serotonergic, they have some good side effects which are the main reason behind their therapeutic effects.
Blockage of 5HT2C serotonin receptors by fluoxetine (Prozac)

 

[aliml]

Serotonin is abundantly released in Covid-19 patients and there is no deficiency.

Platelets Can Associate With SARS-CoV-2 RNA and Are Hyperactivated in COVID-19

Supplemental Digital Content is available in the text.In addition to the overwhelming lung inflammation that prevails in coronavirus disease 2019 (COVID-19), hypercoagulation and thrombosis contribute to the lethality of subjects infected with severe ...

www.ncbi.nlm.nih.gov

 

[Gustav3Y]

It is a 5HT2c antagonist which might explain some of the benefits.

Yes.

 

[Hans]

It is a 5HT2c antagonist which might explain some of the benefits.

It's also a sigma receptor agonist, which has anti-viral effects.

 

[RealNeat]

I think 5HT antagonism might make sense in a dysfunctional system, but doing so in a healthy system makes no sense.

I'm a bit confused with your response. Isn't a dysfunctional system the context we are referring to? Or do you mean cinanserin would be unnecessary in a person with mild symptoms?

 

[Perry Staltic]

I'm a bit confused with your response. Isn't a dysfunctional system the context we are referring to? Or do you mean cinanserin would be unnecessary in a person with mild symptoms?

I was referring to what you said Ray said. If he was referring to correcting an aberrant state, then OK. If not, then what sense does it make to try to increase or decrease serotonin? Leave the body alone to regulate it as it sees fit to maintain health through homeostasis.

 

[Mauritio]

It's also a sigma receptor agonist, which has anti-viral effects.

Sigma 1 ? Then it also has pro-dopamine effects IIRC . Progesterone, testosterone and selegiline all agonize sigma 1 .

 

[Hans]

Sigma 1 ? Then it also has pro-dopamine effects IIRC . Progesterone, testosterone and selegiline all agonize sigma 1 .

Yes. Actually a lot of drugs have sigma 1 receptor agonistic effects, including cypro. I have a list of about 10 "benefits" of prozac and why people get benefits from it which I can post.

 

[Mauritio]

Yes. Actually a lot of drugs have sigma 1 receptor agonistic effects, including cypro. I have a list of about 10 "benefits" of prozac and why people get benefits from it which I can post.

Yes it's quite the interesting receptor . I've been wanting to ask Peat on its significance for some time already .

 

[Diokine]

Modulation of tryptophan metabolism is critical for setting the rate of oxidation/reduction in several dimensions - I think it's intimately involved in generation of tissue environments that are on the spectrum of "self," or cooperative, and "non-self," or destructive. This has obvious implications for immune function. I suspect part of this is mediated through an optical signalling pathway that is active in UV.

I think that tryptophan plays a key role in the coronavirus disease progression, in that disrupting certain aspects of it's regulatory mechanisms is capable of causing catastrophic vascular incompetence. This is is concert with impaired vascular reactivity in the adrenal system, which damages the blood.

From my perspective, serotonin is involved insofar as it tends to sensitize critical TRP channels, allowing for some degree of restoration of feedback in these mechanisms. It is possible to have high serum serotonin, yet be deficient in critical areas. Anti-serotonin measures would probably be effective in treating most symptoms of serious disease progression and probably wouldn't impact the orders of magnitude lower concentrations in nervous tissue like the olfactory system. Like @Hans said, this is more related to disruption of the B0AT1 amino acid transport system.

If you're interested in more of the mechanisms regarding tryptophan, serotonin, and blood, see my thread here.

Coronavirus Infection – ACE2, UV, Tryptophan, And Hemoglobin Oxygen Binding

It's also important to mention the TDO/IDO pathway, and their products kynurenic and quinolinic acids. I suspect these are key players in the previously mentioned "self/non-self" sensing systems, and examination of their structure indicates possible interaction with functional carbonyl groups, implicating the fine tuning of the rate of metabolism as being a critical factor in immune function and tissue differentation.

 

[RealNeat]

I was referring to what you said Ray said. If he was referring to correcting an aberrant state, then OK. If not, then what sense does it make to try to increase or decrease serotonin? Leave the body alone to regulate it as it sees fit to maintain health through homeostasis.

I don't think I've every heard him recommend cinanserin for someone without symptoms.