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Study Shows How NAC Can Help Prevent Strokes


N-acetylcysteine ​​(NAC), a form of the amino acid cysteine ​​and a common dietary supplement, may prevent strokes in people with hereditary cystatin C amyloid angiopathy (HCCAA), a rare genetic disorder.1 People with HCCAA have an average life expectancy of only 30 years and most die within five years of their first stroke.2 therefore reducing their incidence could prove essential to increase survival.

The discovery is even more significant because it was led by researchers at Children’s Hospital of Philadelphia (CHOP), which is notoriously against supplements.3 NAC appears to work by preventing the formation of amyloid-producing proteins, which promote amyloid deposits associated with stroke.4

Preventing Stroke Could Save Lives Of People With HCCAA

HCCAA belongs to a group of diseases called cerebral amyloid angiopathies (AAC), in which amyloid deposits form in the blood vessels of the central nervous system.

Amyloid deposits are also implicated in a number of other neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Creutzfeldt-Jacob and Huntington’s diseases.5 HCCAA is an inherited disease, caused by a leucine 68 glutamine variant of human cystatin C known as L68Q-hCC.

Young carriers of the mutation suffer from micro-infarcts, which are microscopic lesions, or areas of cell death or tissue necrosis,6 associated with cognitive impairment in the elderly.7 Micro-brain infarctions are clinical markers of stroke and dementia.8

In people with HCCAA, microinfarctions start in their twenties with brain hemorrhages, leading to paralysis, dementia and – as strokes become more frequent – death.9 Deposits of hCC are primarily found in the brains of people with HCCAA, although they can also be found in other internal organs.

The study by CHOP researchers suggests that NAC could block the precipitation of amyloid plaque deposits and help break down their formation, which could make a dramatic difference for people with HCCAA. Lead author of the study, Dr Hakon Hakonarson, director of the Center for Applied Genomics at CHOP, said in a press release:ten

“Amyloids cannot precipitate without aggregating, so if we can prevent this aggregation with a drug [NAC] that is already available, then we could make an incredible difference in the lives of these patients.

Additionally, since we already have genetic testing to identify these patients, we could potentially administer this treatment early in life and potentially prevent the first stroke from occurring.

CNA May Help Prevent Stroke

The CNA is best known to help increase glutathione and reduce the toxicity of acetaldehyde11 which causes many symptoms of hangovers. Anyone who overdoses on acetaminophen (Tylenol) also receives high doses of NAC in the emergency room, as it helps prevent liver damage by increasing glutathione.

NAC is also sometimes prescribed to break up mucus in the lungs,12 and CHOP researchers used NAC to treat cell lines expressing wild-type and mutant L68Q hCC, to determine its effects on toxic oligomers that occur in several types of amyloidosis.

NAC broke the oligomers into monomers (oligomers are made up of a few monomer units13), which helps prevent the formation of amyloid deposits associated with stroke.14 “Based on the results of the cellular work described, it became evident that NAC could be useful in treating this devastating disease,” the researchers wrote in Nature Communications.15

NAC was also evaluated in six patients with the L68Q-hCC variant who were taking NAC. The variant is believed to originate from a mutation in the Icelandic population that occurred in the 16th century. The proband – the person who was the starting point of the familial genetic study – of an HCCAA family in Iceland had suffered three severe strokes over a nine-month period at the age of 22.

The person was put on a ventilator after the third stroke and suffered from mucus obstruction, but was treated with NAC, which gradually resolved the mucus obstruction. Due to the positive cell model results, the person continued to take NAC, as did five family members who also carried the mutation.

Because the impacts of NAC on hCC deposition in the brain cannot be directly monitored, the researchers performed skin biopsies on all six individuals. Research suggests that amyloid deposits in the skin correlate with symptom status in patients with HCCAA, with those with symptoms having a higher deposit in the skin.16

Up to 90% reduction of L68Q-hCC after NAC

Skin biopsies showed that five of six patients had a 50% to 90% reduction in hCC protein complex deposition after NAC supplementation – a dramatic result. The researchers wrote:17

“[T]The proband had very high levels of hCC protein complex deposition during the first skin biopsy. Subsequent biopsies reveal that the proband has not progressed in terms of deposition; on the contrary, the deposit had decreased by about 40%.

… The reduction in hCC deposition in the proband from the first biopsy to the third (approximately 15 months at two different doses) was estimated to be ~ 70%… The parent demonstrated a ~ 50% reduction in staining on the biopsy n ° 3… and the brother ~ 30% after 6 months of NAC.

In the second cohort, carriers 1 and 2 showed a visible reduction in hCC deposition with carrier 1 having almost complete clearance after 600 mg NAC 3 x daily for 24 months.

… Treatment with NAC in human patients not only prevents the continued deposition of the protein cystatin C complex in the skin, but also significantly reduces previous deposition.

A NAC clinical trial was launched in 2019 to determine if the results will be confirmed in more subjects, with results expected in the second quarter of 2021.

The many advantages of the CNA

In the case of HCCAA, the average lifespan of those affected has dropped dramatically from around 65 years in 1825 to around 30 years in 2021. Lifestyle, economic and industrial changes have all been suggested as factors. contributing to this decline, including the increase in the consumption of carbohydrates in the diet. This theory matches the NAC showing an advantage, as the researchers noted:18

Hyperglycemia has been linked to oxidative stress in diabetes, and it is possible that the increase in carbohydrates in Icelandic diets in the 19th century created enough oxidative stress in L68Q-hCC carriers to worsen the presentation of the disease. .

This assumption is compatible with our results; increased oxidative stress would increase multimerization of L68Q-hCC, and food reducing agents such as NAC would reverse this effect and prevent deposition of new aggregates. The therapeutic benefits would come mainly from the absence of new occlusions causing new strokes. “

While the most common use of NAC is for liver support, it also shows increasing promise as a neuroprotector. In addition to HCCAA, scientists are studying NAC as a treatment for Parkinson’s disease, which has been linked to a deficiency of glutathione in substantia nigra, a region that harbors dopaminergic neurons.19

NAC is a precursor and a nutrient limiting the rate of glutathione formation;20 because glutathione is poorly absorbed, in many cases it is easier to increase your glutathione by taking NAC instead.

It could also have potential for Alzheimer’s disease because, according to researchers at CHOP, the process of protein deposition that occurs in HCCAA is similar to what happens in Alzheimer’s disease, although to a accelerated rate in HCCAA compared to Alzheimer’s disease, which is why dementia occurs later in life with the latter.

“If the mechanisms underlying protein deposition and pathogenesis are similar enough, similar or identical treatments can be effective,” they said.21 Another area in which NAC holds particular promise is the treatment of mental health disorders, including post-traumatic stress disorder.22 depression23 and substance use disorders.24

The NAC even shows promise for COVID-19. According to an analysis of the literature,25 Glutathione deficiency may be associated with the severity of COVID-19, leading the author to conclude that NAC may be useful for both its prevention and treatment.

NAC can also fight the abnormal blood clotting seen in many cases and helps release thick mucus in the lungs. Interestingly, with COVID-19 treatment as a new indication, the United States Food and Drug Administration suddenly suppressed NAC, claiming that it is excluded from the definition of a dietary supplement because it was approved as a new drug in 1985.26

As such, NAC cannot technically be marketed as a supplement, even though there are no less than 1,170 products containing NAC in the National Institutes of Health’s Dietary Supplement Label Database. .27

Why the CHOP study is of additional importance

The fact that CHOP researchers recommend NAC for the treatment of HCCAA is particularly important given their historical opposition to the use of dietary supplements. In October 2013, it announced that its list of drugs approved for use would no longer include most dietary supplements, making it the first U.S. hospital to discourage its patients from using dietary supplements on principle.28

Their reasoning was that dietary supplements are “essentially unregulated” with “no solid information” about side effects, drug interactions, or standard dosage, which they said made giving them to sick children “contrary to the law. ethics when the risks are unknown ”. But given the results of the recent study, it would be unethical to refuse such potentially life-saving treatment.

The policy is so strict that parents are advised to admit their child if they take any supplements. The use of supplements is therefore not recommended, parents being informed in particular of the hospital’s anti-supplementation policy and the risks associated with supplements, and if “after receiving this information, a parent or guardian insists on continuing to give to their child a food supplement ”, they must sign a waiver to this effect.

Only a limited list of “acceptable products” is allowed in the CHOP supplement form, and it is not clear if NAC is one of them. If not, it is certainly worth adding, and perhaps the study will open CHOP’s eyes to the life-saving potential of natural products and dietary supplements.



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