Tetracyclines Cause Mitochondrial Dysfunction

[Logan-]

Knowing the basics of the origin and evolution of the cells, I asked myself this question: "How do antibiotics affect human mitochondrial function?"


First, read this: Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. The Origin and Evolution of Cells.

Endosymbiosis: Symbiogenesis - Wikipedia
Endosymbiosis and The Origin of Eukaryotes
https://evolution.berkeley.edu/evoli...dosymbiosis_04


Indeed, mitochondria, the organelles responsible for energy production in the cell, have bacteria-like DNA and other molecules, suggesting that mitochondria are the product of an ancient endosymbiotic event, in which a bacterium was engulfed by another cell. The important implication of this, said Ronald DePinho, president of the MD Anderson Cancer Centre in Houston, Texas, who also did not participate in the research, is that “drugs targeted to [bacterial] physiology might also impinge on mitochondrial biology.”

and a comment [1] on this report:

In additon to the disruption of normal ROS signalling pathways mentioned in this paper many antibiotics have two other deleterious effects in human cells. They decrease respiratory competence and shift cell populations to aerobic glycolysis (the Warburg effect) resulting in localized lactic acidosis and a microenviroment favorable to tumor formation, tissue invasion and metastasis. In addition increased poduction of ROS is mutagenic to both nDNA and mtDNA destabilizing both genomes, decreasing mitochondrial survellance and clearing of tumorigenic karyotypes in the nucleus by the intrinsic apoptotic pathway, both hallmark features of cancer. I suggest (in agreement with many other investigators) that such antibiotics are carcinogenic and thus the findings reported here are very clinically relevant especially when administered for chronic infection. We need to find alternative antimicrobial therapies for non life threatening infections that do not harm these patients.

http://www.the-scientist.com/?articl...-Antibiotics-/

From:http://www.the-scientist.com/?articl...-Mitochondria/


Kalghatgi S, Spina CS, Costello JC, et al. Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells. Science translational medicine. 2013;5(192):192ra85. doi:10.1126/scitranslmed.3006055.
Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells. - PubMed - NCBI


(a MD's review of the above study)


Stefano GB, Samuel J, Kream RM. Antibiotics May Trigger Mitochondrial Dysfunction Inducing Psychiatric Disorders. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2017;23:101-106. doi:10.12659/MSM.899478.
Antibiotics May Trigger Mitochondrial Dysfunction Inducing Psychiatric Disorders


Reactive Species Contribute to Antibiotic-Mediated Killing
Reactive Species Contribute to Antibiotic-Mediated Killing


Antibiotic and ROS linkage questioned
https://www.nature.com/articles/nbt.2574


Moullan N, Mouchiroud L, Wang X, Ryu D, Williams EG, Mottis A, Jovaisaite V, Frochaux MV, Quiros PM, Deplancke B, Houtkooper RH, Auwerx J (2015). "Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research". Celll Reports. 10 (10): 1681–91. doi:10.1016/j.celrep.2015.02.034. PMID 25772356.
http://www.cell.com/cell-reports/pdf/S2211-1247(15)00180-1.pdf


Chatzispyrou IA, Held NM, Mouchiroud L, Auwerx J, Houtkooper RH (2015). "Tetracycline antibiotics impair mitochondrial function and its experimental use confounds research". Cancer Research. 75 (21): 4446–9. doi:10.1158/0008-5472.CAN-15-1626. PMID 26475870.


Wang X, Ryu D, Houtkooper RH, Auwerx J. Antibiotic use and abuse: A threat to mitochondria and chloroplasts with impact on research, health, and environment. Bioessays. 2015;37(10):1045-1053. doi:10.1002/bies.201500071.
Antibiotic use and abuse: A threat to mitochondria and chloroplasts with impact on research, health, and environment



Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, et al. 2007. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130: 797–810. [PubMed]
http://www.cell.com/cell/pdf/S0092-8674(07)00899-9.pdf

Ahler E, Sullivan WJ, Cass A, Braas D, York AG, et al. (2013) Doxycycline Alters Metabolism and Proliferation of Human Cell Lines. PLOS ONE 8(5): e64561. Doxycycline Alters Metabolism and Proliferation of Human Cell Lines


General info on bactericidal and bacteriostatic distinction in antibiotics: https://courses.lumenlearning.com/bo...obial-therapy/


Is there anything we can do to counter these harmful effects?

If the sole mechanism behind antibiotics’ disruption of mitochondrial function is through oxidative stress, then taking antioxidants like vitamin E, and doing things that support endogenous antioxidants during the antibiotic course could reduce the damage.

There is an “all positive” view of antibiotic usage in this community. My purpose in creating this thread is to open that view into discussion.

Regards

Logan

[1]: The comment below was added under the report by a reader. It appears the website has deleted the comments section from the web page. I had saved this comment when I first read this report a few months ago.

 

[Logan-]

@haidut @Travis @tyw @Amazoniac

 

[Logan-]

Could you share your opinions about this?

 

[SOMO]

I took Doxycycline (for acne) and got diarrhea and lost almost 10 lbs in a week (was already underweight.)

 

[Waynish]

@Logan- which antibiotics do you believe this applies to, if not all?

 

[Vinero]

I took Doxycycline (for acne) and got diarrhea and lost almost 10 lbs in a week (was already underweight.)

That can also be caused by the additives like silicon dioxide, titianium dioxide etc. which can be present in the doxycycline pill. I have taken pure doxycycline without additives and had none of those effects, or any bad effects on digestion whatsoever. When I took regular doxycycline from the pharmacy which has a lot of additives, I got intestinal problems like you describe.

 

[Suikerbuik]

I think this applies to all antibiotics, but the dose makes the poison. Hence Ray advices relatively low doses.
I think minocycline, peniciline, doxycycline, azithromycine, amoxicilline, clindamycine should all be relatively safe. I have had minocycline, amoxicilline and doxycycline in the past (on doctors prescription for (presumed) infections and not bacteria reduction); so I don't know what the other antibiotics feel like.

 

[Logan-]

@Logan- which antibiotics do you believe this applies to, if not all?

You can look at the studies and articles I provided in the OP for the antibioitcs, I think this is still a new area of interest and there aren't many studies with different antibiotics.

There is also other factors like the antibiotic dosage, treatment duration, usage of more than one antibiotics together in one course, host's kidney and liver function, hydration level etc. that all affect the bacteriostatic-bactericidal character of the antibiotics that are being used.

 

[Logan-]

I think the issue could be more than the bacteriostatic and bactericidal distinction, and each antibiotic group should be studied for this effect.

For example, tetracyclines are known to be bacteriostatic in relevant dosages; not bactericidal.
Antagonism between Bacteriostatic and Bactericidal Antibiotics Is Prevalent

 

[Logan-]

Antibiotics

Bactericidal antibiotics kill bacteria; bacteriostatic antibiotics slow their growth or reproduction.

Bactericidal antibiotics that inhibit cell wall synthesis: the beta-lactam antibiotics (penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems) and vancomycin.

Also bactericidal are daptomycin, fluoroquinolones, metronidazole, nitrofurantoin, co-trimoxazole, telithromycin.

Aminoglycosidic antibiotics are usually considered bactericidal, although they may be bacteriostatic with some organisms

The distinction between bactericidal and bacteriostatic agents appears to be clear according to the basic/clinical definition, but this only applies under strict laboratory conditions and it is important to distinguish microbiological and clinical definitions.[2] The distinction is more arbitrary when agents are categorized in clinical situations. The supposed superiority of bactericidal agents over bacteriostatic agents is of little relevance when treating the vast majority of infections with gram-positive bacteria, particularly in patients with uncomplicated infections and noncompromised immune systems. Bacteriostatic agents have been effectively used for treatment that are considered to require bactericidal activity. Furthermore, some broad classes of antibacterial agents considered bacteriostatic can exhibit bactericidal activity against some bacteria on the basis of in vitro determination of MBC/MIC values. At high concentrations, bacteriostatic agents are often bactericidal against some susceptible organisms. The ultimate guide to treatment of any infection must be clinical outcome.

Bactericide - Wikipedia


Here's a list, if anyone wants to see:

TABLE 1
List of all antibiotics used in the study

Abbreviation Antibiotic EC90a (μg/ml) Main mechanism of action Bactericidal/bacteriostatic status
AMP Ampicillin 1.2 Cell wall Bactericidal
PIP Piperacillin 1.5 Cell wall Bactericidal
FOX Cefoxitin 1.4 Cell wall Bactericidal
FOS Fosfomycin 14 Cell wall Bactericidal
LOM Lomefloxacin 0.12 Gyrase Bactericidal
CPR Ciprofloxacin 0.0055 Gyrase Bactericidal
NAL Nalidixic acid 2.3 Gyrase Bactericidal
FSM Fosmidomycin 40 Lipid Bactericidal
NIT Nitrofurantoin 2.4 Multiple mechanisms Bactericidal
AMK Amikacin 3.4 Aminoglycoside, 30S protein synthesis Bactericidal
GEN Gentamicin 0.66 Aminoglycoside, 30S protein synthesis Bactericidal
KAN Kanamycin 3 Aminoglycoside, 30S protein synthesis Bactericidal
TOB Tobramycin 0.85 Aminoglycoside, 30S protein synthesis Bactericidal
STR Streptomycin 4.5 Aminoglycoside, 30S protein synthesis Bactericidal
TET Tetracycline 0.3 30S protein synthesis Bacteriostatic
DOX Doxycycline 0.23 30S protein synthesis Bacteriostatic
CHL Chloramphenicol 1 50S protein synthesis Bacteriostatic
ERY Erythromycin 8.5 50S protein synthesis Bacteriostatic
FUS Fusidic acid 200 50S protein synthesis Bacteriostatic
SLF Sulfamonomethoxine 1.9 Folic acid biosynthesis Bacteriostatic
TRM Trimethoprim 0.4 Folic acid biosynthesis Bacteriostatic
aEC90 represents the concentration of an antibiotic at which 90% of the maximal growth inhibitory effect was observed.

Antagonism between Bacteriostatic and Bactericidal Antibiotics Is Prevalent

 

[koky]

vinero how did you find/get additive free antibiotics?

 

[TheHound]

was prescribed amoxicillin for a throat infection almost a month ago. pleasant side effect from it was that it completely (and i mean 100%) eliminated acne. Told my doctor this and he prescribed me doxycycline 100mg tablets last week which I've taken a few times. still keeps the acne away completely and no side effects. I'll probably take it sporadically

 

[Logan-]

An earlier discussion about this topic: The Tetracycline Antibiotics Inhibit Mitochondrial Respiration

 

[accelerator]

That can also be caused by the additives like silicon dioxide, titianium dioxide etc. which can be present in the doxycycline pill. I have taken pure doxycycline without additives and had none of those effects, or any bad effects on digestion whatsoever. When I took regular doxycycline from the pharmacy which has a lot of additives, I got intestinal problems like you describe.

Where can one get pure doxycycline?

 

[yerrag]

Antibiotics

Bactericidal antibiotics kill bacteria; bacteriostatic antibiotics slow their growth or reproduction.

Bactericidal antibiotics that inhibit cell wall synthesis: the beta-lactam antibiotics (penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems) and vancomycin.

Also bactericidal are daptomycin, fluoroquinolones, metronidazole, nitrofurantoin, co-trimoxazole, telithromycin.

Aminoglycosidic antibiotics are usually considered bactericidal, although they may be bacteriostatic with some organisms

The distinction between bactericidal and bacteriostatic agents appears to be clear according to the basic/clinical definition, but this only applies under strict laboratory conditions and it is important to distinguish microbiological and clinical definitions.[2] The distinction is more arbitrary when agents are categorized in clinical situations. The supposed superiority of bactericidal agents over bacteriostatic agents is of little relevance when treating the vast majority of infections with gram-positive bacteria, particularly in patients with uncomplicated infections and noncompromised immune systems. Bacteriostatic agents have been effectively used for treatment that are considered to require bactericidal activity. Furthermore, some broad classes of antibacterial agents considered bacteriostatic can exhibit bactericidal activity against some bacteria on the basis of in vitro determination of MBC/MIC values. At high concentrations, bacteriostatic agents are often bactericidal against some susceptible organisms. The ultimate guide to treatment of any infection must be clinical outcome.

Bactericide - Wikipedia


Here's a list, if anyone wants to see:

TABLE 1
List of all antibiotics used in the study

Abbreviation Antibiotic EC90a (μg/ml) Main mechanism of action Bactericidal/bacteriostatic status
AMP Ampicillin 1.2 Cell wall Bactericidal
PIP Piperacillin 1.5 Cell wall Bactericidal
FOX Cefoxitin 1.4 Cell wall Bactericidal
FOS Fosfomycin 14 Cell wall Bactericidal
LOM Lomefloxacin 0.12 Gyrase Bactericidal
CPR Ciprofloxacin 0.0055 Gyrase Bactericidal
NAL Nalidixic acid 2.3 Gyrase Bactericidal
FSM Fosmidomycin 40 Lipid Bactericidal
NIT Nitrofurantoin 2.4 Multiple mechanisms Bactericidal
AMK Amikacin 3.4 Aminoglycoside, 30S protein synthesis Bactericidal
GEN Gentamicin 0.66 Aminoglycoside, 30S protein synthesis Bactericidal
KAN Kanamycin 3 Aminoglycoside, 30S protein synthesis Bactericidal
TOB Tobramycin 0.85 Aminoglycoside, 30S protein synthesis Bactericidal
STR Streptomycin 4.5 Aminoglycoside, 30S protein synthesis Bactericidal
TET Tetracycline 0.3 30S protein synthesis Bacteriostatic
DOX Doxycycline 0.23 30S protein synthesis Bacteriostatic
CHL Chloramphenicol 1 50S protein synthesis Bacteriostatic
ERY Erythromycin 8.5 50S protein synthesis Bacteriostatic
FUS Fusidic acid 200 50S protein synthesis Bacteriostatic
SLF Sulfamonomethoxine 1.9 Folic acid biosynthesis Bacteriostatic
TRM Trimethoprim 0.4 Folic acid biosynthesis Bacteriostatic
aEC90 represents the concentration of an antibiotic at which 90% of the maximal growth inhibitory effect was observed.

Antagonism between Bacteriostatic and Bactericidal Antibiotics Is Prevalent

I've been taking doxycyline for a while and I'm thinking of changing to another antibiotic. I've been monitoring my body temperature, and notice it lowering from 37C to as low as 36.1, but it's since come up to 36.6. It's possible that it's having an effect on my mitochondrial cells. I'm not really sure, but it could also be because of other substances (mostly biofilm busters) I'm taking, but it's better to be safe as this is a red flag.

As I'm dealing with p. gingivalis, a periodontal bacteria, I have the following to choose from, which I came across reading this review (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405727/pdf/zjom-9-1300366.pdf):

erythromycin (macrolides)
climdamycin (lincosadimes)
ampicillin, amoxicillin (b-lactams)
metronidazole (nitroimidozoles)

I'm thinking of changing to erythromycin. Would this be a good choice as it's bacteriostatic, just like doxycycline?

At my current dosage of 2x50mg doxy, what would be the equivalent dosage with erythromycin?

 

[Tarmander]

I've been taking doxycyline for a while and I'm thinking of changing to another antibiotic. I've been monitoring my body temperature, and notice it lowering from 37C to as low as 36.1, but it's since come up to 36.6. It's possible that it's having an effect on my mitochondrial cells. I'm not really sure, but it could also be because of other substances (mostly biofilm busters) I'm taking, but it's better to be safe as this is a red flag.

As I'm dealing with p. gingivalis, a periodontal bacteria, I have the following to choose from, which I came across reading this review (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405727/pdf/zjom-9-1300366.pdf):

erythromycin (macrolides)
climdamycin (lincosadimes)
ampicillin, amoxicillin (b-lactams)
metronidazole (nitroimidozoles)

I'm thinking of changing to erythromycin. Would this be a good choice as it's bacteriostatic, just like doxycycline?

At my current dosage of 2x50mg doxy, what would be the equivalent dosage with erythromycin?

Erythro is one of the best feeling antibiotics I ever took. Super safe too.

equivalent would be 250mg per day. Usual dose of doxy is 100mg x2 per day. For erythro it’s 250mg x2 I believe

 

[yerrag]

Erythro is one of the best feeling antibiotics I ever took. Super safe too.

equivalent would be 250mg per day. Usual dose of doxy is 100mg x2 per day. For erythro it’s 250mg x2 I believe

Thanks! I was afraid to go 100mg x2 on doxy for say, a month. Perhaps I should and not worry about the bacteria developing a resistance to it.

Now I'll go to a higher equivalent dosage with erythromycin, considering that my periodontal bacterial colony is no pushover.

 

[Tarmander]

Thanks! I was afraid to go 100mg x2 on doxy for say, a month. Perhaps I should and not worry about the bacteria developing a resistance to it.

Now I'll go to a higher equivalent dosage with erythromycin, considering that my periodontal bacterial colony is no pushover.

I know you are doing systemic enzymes. Have you ever tried Lumbrokinase? 30x more powerful then nattokinase

 

[yerrag]

I know you are doing systemic enzymes. Have you ever tried Lumbrokinase? 30x more powerful then nattokinase

Have never heard of it. Will check on it and try. Have been using ZymEssence of Dr. Wong's. Used Serrapeptidase as well.

Felt that ZymEssence does a steady job of lysing plaque without overkill. Serrapeptidase, at the dosage of 160,000 IU per capsule, was overkill. At least for my needs. Too much lysing power that it releases too much bacteria from the biofilms in my blood vessel linings. Could overwhelm my system.

 

[Tarmander]

Have never heard of it. Will check on it and try. Have been using ZymEssence of Dr. Wong's. Used Serrapeptidase as well.

Felt that ZymEssence does a steady job of lysing plaque without overkill. Serrapeptidase, at the dosage of 160,000 IU per capsule, was overkill. At least for my needs. Too much lysing power that it releases too much bacteria from the biofilms in my blood vessel linings. Could overwhelm my system.

Check out this paper. Scroll down to lumbrokinase(page 4) unless you want to know a lot about earth worms. I am researching a podcast on it.

Lumbro, unlike the other systemic enzymes, seems to stabilize the fibrogen system. So it avoids some of the side effects of the other enzymes. Also has possible anti bacteria/anti biofilm effects