The 10+ Benefits of Beta-Lactam Antibiotics And Ceftriaxone

Ceftriaxone Regulates Glutamate Transporters

I usually advise to stay away from all antibiotics, but I've had clients that have had profoundly beneficial experiences with certain β-lactam antibiotic (see below). 

I will only briefly talk about their anti-microbial action in this post and will mostly be talking about rocephin (Ceftriaxone).

I think the downsides to antibiotics are well known (like antibiotic resistance, killing the microbiome, mitochondrial disruption) so that is not my main focus of this post - all those are discussed in my antibiotics post.

So I will be discussing some promising benefits.

Contents:

  1. Basics
  2. Benefits Of Beta-Lactam Antibiotics
  3. My Client's Experience With Beta-Lactam Antibiotics
  4. Caveats Of Beta-Lactam Antibiotics
  5. Alternatives And What To Do If You Go On A Beta-Lactam Antibiotic
  6. Mechanism Of Action
  7. More Research

Basics

Beta-lactam antibiotics are a class of broad-spectrum antibiotics. R

 
 

As shown in this picture, they simply contain a beta-lactam ring in their molecular structures. R

This includes penicillin derivatives (penams), cephalosporins (cephems like ceftriaxone), monobactams, and carbapenems. R

Although they do have anti-microbial activities, beta-lactam antibiotics also have effects on the central nervous system and may be beneficial for: R

  • Addiction
  • Amyotrophic Lateral Sclerosis (ALS)
  • Epilepsy
  • Parkinson's Disease (PD) 
  • Stroke

Benefits Of Beta-Lactam Antibiotics

1. Protects The Brain After Stroke

 
 

The beta-lactam antibiotic, ceftriaxone (CF) is neuroprotective during traumatic brain injuries (TBI). R

For example, in a rodent model of TBI, CF improves post-injury outcomes by decreasing excess glutamate. R

In the hippocampus, CF protects hippocampal neurons from death. R

CF reduces post traumatic astrogliosis (an increase in brain immune cells that destroy neurons) 7 days after TBI. R

A single dose of CF after TBI helps protect against learning and spacial memory deficits. R

CF may also decrease the amount of fluid after a hemorrhagic stroke and reduce inflammation. R R

2. May Help With Epilepsy

Epilepsy is common after TBI as neuronal death creates excess glutamate which triggers epilepsy.  R

From excess glutatmate, epilepsy causes oxidative stress such as reactive oxygen species (ROS), which reduces antioxidants such as glutathione (GSH) in the brain. R

CF decreases oxidative stress by decreasing glutamate and free radicals. R

In animal models 12 weeks after TBI, CF reduces both seizure frequency and duration. R

In studies where rats that given a toxin to induce seizures (pentylenetetrazole), CF was able to reduce oxidative stress in the hippocampus.  R

3. May Help With Alzheimer's Disease

In animals genetically engineered to age poorly, CF helps protect the hippocampus and prevented cognitive decline. R

CF is also able to ameliorate tau tangles and inhibit cognitive decline in mouse models of Alzheimer's Disease (AD). R

CF also helps increase synaptic plasticity in mice genetically altered to have problems with glutamate. R 

Although, CF may decrease long term potentiation (LTP), which may result in reduced spatial learning and memory impairment. R R

LTP impairment is commonly seen in patients with AD. R

4. May Help With Autism Spectrum Disorders

Autism Spectrum Disorders (ASD) consist of neuroinflammation and one reason for this is because of excess glutamate. 

CF may be able to balance neuroinflammation (glutamate and ammonia) in ASD, possibly helping Rett's syndrome as well. R

5. May Help With Amyotrophic Lateral Sclerosis

In models of Amyotrophic Lateral Sclerosis (ALS), CF also delays neuronal loss by protecting against glutamate excitotoxicity (common in ALS). R

6. May Help With Multiple Sclerosis

In animal models of multiple sclerosis, CF reduced the severity of pain and delayed motor weakness and paralysis. R

7. May Help With Huntington’s Disease

In animal models of Huntington's Disease (HD), CF improves behavioral performance. R

8. May Help With Depression

By regulating glutamate, CF has antidepressant-like effects in animal models of depression. R

9. May Help With Addiction, Dependence and Tolerance

 
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CF may help with addiction and dependence in:

  • Alcohol R R
  • Amphetamines R
  • Cocaine (reducing tolerance) R R R
  • Heroin R
  • Nicotine R 
  • Sugar R

For example, CF can inhibit animals desire to self-administer cocaine, alcohol, and heroin seeking. R

CF may also reverse tolerance to drugs (such as opiates and stimulants). R R

10. May Help With Parkinson's Disease

Levodopa (L-Dopa) is commonly used to treat Parkinson's Disease (PD), but can cause side effects such as dyskinesia (involuntary movements). R

CF may help with dyskinesia by reducing the exicotoxic effects of L-Dopa. R

In animal models of PD that were subjected to MPTP (chemical used to induce PD in animals), CF helped restore brain-derived neurotropic factor (BDNF) and improve memory. R R R

My Client's Experience With Beta-Lactam Antibiotics

The client I was working with had suffered a hemorrhagic stroke.

She couldn't:

  • Remember names
  • Identify where she was
  • Properly form words (or sentences)

We had her take only 1g 2x/wk intramuscular injections of rocephin (beta-lactam antibiotic known as ceftriaxone) over a few weeks.

Honestly, she came back to life.

She could walk (with physical therapy assistance), her speech improved, and she was able to hold conversations.

She was even able to perform certain brain-training games with me – it was spectacular!

Caveats Of Beta-Lactam Antibiotics

Biofilm formation, antibiotic resistance, mitochondrial dysfunction, dybiosis and microbiome problems (leading to cognitive problems from gut-brain axis dysfunction) are problems with beta-lactam antibiotics (all of this can be read about on the antibiotics post). R R 

CF can cause biliary sludge, hyperbilirubinemia, pseudolithiasis, liver damage and hemolytic anemia, so it's best not to take it if you have biliary problems (gallbladder/liver/pancreas). R R R R

CF upregulates cytochrome P450 in the liver, so it could contradict with other drugs that work on that pathway. R

Also, beta-lactamase enzymes may break down beta-lactam antibiotics. R

Beta-lactam antibiotics cross the blood brain barrier (although penicillin isn't strong) and can interfere with brain development in the womb, so it's best to avoid during pregnancy. R

It's important to note that glutamate transporters (CF upregulates it) may be (paradoxically) a major source of toxic accumulation of extracellular glutamate after injury, when the transporters operate in reverse, which is dependent on glutamate transporter stoichiometry and transmembrane sodium and potassium concentration gradients. R

I'd also like to add that I am allergic to beta-lactam antibiotics, which is very common. R R R

Alternatives And What To Do If You Must Go On A Beta-Lactam Antibiotic

 
 

Maslinic acid enhances glutamate clearance, increases EAAT2 protein/mRNA levels, prevents glutamate toxicity, reduces infarct volumes in stroke, and improves neurological scores in vitro and in vivo. R

N-Acetyl-Cysteine (NAC) combines well with CF during stroke. R

Jujube can also help protect the brain against excitotoxicity by beta-lactam antibiotics. R

Gastrodin and phenytoin (drug) can protect against cognitive problems with penicillin. R

Mechanism Of Action

Simple:

  • Increases Caspace-9 R
  • Increases EAAT2 (GLT-1 in rodents) R R R
  • Increases GSH R
  • Increases NRF2 R
  • Increases pAKT R
  • Increases xCT R
  • Restores BDNF R
  • Decreases FasL R
  • Decreases IL-1b R
  • Decreases LC3 II R
  • Decreases MMP9 R
  • Decreases TNF-a R

Advanced:

  • Beta-lactam antibiotics (ampicillin, cefazolin, clavulanate and cefoperazone) upregulate both EAAT2 and pAKT levels in the NAc, PFC, and VA (preventing glutamate neurotoxicity and restoring glutamate to normal levels), while inhibiting hepatic ALDH2. R R R R R
  • CF also regulates glutamate and dopamine by binding to metallo-beta-lactamase domain containing 1 (MBLAC1). R
  • Sulbactam prevents decrease in EAAT2 expression after stroke and protects CA1 pyramidal cells from neural death after stroke. R
  • Beta-lactam antibiotics are eliminated in urine (via PAH in the kidneys) and bile (excreted in feces), has a half life of 6-9h, goes throughout the body including the brain (esp. when meninges are inflamed), and crosses blood-brain barrier very easily (except for penicillin). R R
  • CF increases system XC activity (XCT, rate-limited step in the synthesis of cysteine to produce glutathione (GSH)) - normalizing extraellular glutamate uptake and increasing expression of antiproter via increased NRF2 levels -> increasing intracellular GSH. R
  • By doing this it upregulates NF-kB (by degrading cytoplasmic inhibitor proteins normally bound to NF-kB, liberating NF-kB) and ARE-1. R R
  • β-Lactam antibiotics affect platelet activation through interaction with platelet surface receptors (and may be irreversible). R R
  • In parkinson's models, CF balances glutamate and tyrosine hydroxylase (TH). R
  • In addiction models, CF acts on AMPA and kainate as well as NMDA. R R R

More Research

  • CF can reduce serotonin-induced scratching behavior. R