'; Study Shows How NAC Can Help Prevent Strokes – Dr Fundile Nyati

Study Shows How NAC Can Help Prevent Strokes

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 just 30 years, and most die within five years of their first stroke,2 so reducing their incidence could prove to be essential to increasing survival.

The finding is even more significant because it was conducted by researchers from 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 linked to strokes.4

Preventing Strokes Could Save the Lives of Those With HCCAA

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

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

Young people with the mutation suffer from microinfarcts, which are microscopic lesions, or areas of cellular death or tissue necrosis,6 that are associated with cognitive impairment in older adults.7 Cerebral microinfarcts are clinical markers for stroke and dementia.8

In people with HCCAA, the microinfarcts begin in their 20s along with brain hemorrhages, leading to paralysis, dementia and — as the strokes become more frequent — death.9 hCC deposits are found primarily in the brain in those with HCCAA, though they may also be found in other internal organs.

The study by CHOP researchers suggests NAC may block the precipitation of amyloid plaque deposits, as well as help break up their formation, which could make a dramatic difference for those living with HCCAA. The study’s lead author, Dr. Hakon Hakonarson, director of CHOP’s Center for Applied Genomics, said in a news release:10

“Amyloids cannot precipitate without aggregating, so if we can prevent that 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 available to identify these patients, we could conceivably give this treatment early in life and potentially prevent that first stroke from ever occurring.�

NAC May Help Prevent Strokes

NAC is most well-known to help increase glutathione and reduce the acetaldehyde toxicity11 that causes many hangover symptoms. Anyone who overdoses on acetaminophen (Tylenol) also receives large 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 the CHOP researchers used NAC to treat cell lines expressing wild type and L68Q-mutant hCC, to determine its effects on toxic oligomers that occur in multiple types of amyloidosis.

NAC broke the oligomers into monomers (oligomers are composed of a few monomer units13), which helps prevent the formation of amyloid deposits linked to strokes.14 “Given the results from the described cellular work, it became evident that NAC could potentially be useful to treat 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 thought to stem from a mutation in the Icelandic population that occurred during the 16th century. The proband — the person who was the starting point for the family genetic study — from one HCCAA family in Iceland had suffered from three serious strokes over a nine-month period at the age of 22.

The person was put on a respirator after the third stroke and was suffering from mucus plugging, but was treated with NAC, which gradually resolved the mucus plugging. Due to the positive results from the cellular models, the person continued to take NAC, as did five family members who were also carriers of the mutation.

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

Up to 90% Reduction in L68Q-hCC After NAC

The skin biopsies showed that five of the six patients had a 50% to 90% reduction of hCC protein complex deposition following NAC supplementation — a dramatic result. The researchers wrote:17

“[T]he proband had very high levels of hCC protein complex deposition in the first skin biopsy. Subsequent biopsies reveal the proband had not progressed in terms of deposition; rather, the deposition had decreased by about 40%.

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

In the second cohort, carriers 1 and 2 showed a visible reduction in the hCC deposition with carrier 1 having near-complete clearance following 600 mg of NAC 3× per day for 24 months.

… Treatment with NAC in human patients not only prevents ongoing deposition of cystatin C protein complex in the skin, but also reduces prior deposits in a significant way.�

An NAC clinical trial was launched in 2019 to investigate whether the results will be confirmed in a larger number of subjects, with results expected in the second quarter of 2021.

The Many Benefits of NAC

In the case of HCCAA, the average lifespan of those affected has dropped significantly, from approximately 65 years in 1825 to about 30 years in 2021. Lifestyle, economic and industrial changes have all been suggested as contributing factors to this decline, including increased consumption of carbohydrates in the diet. This theory fits with NAC showing a benefit, as the researchers noted:18

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

This hypothesis is compatible with our results; increased oxidative stress would increase multimerization of L68Q-hCC, and dietary reducing agents like NAC would reverse that effect and prevent deposition of new aggregates. Therapeutic benefits would be derived mainly from the lack of new occlusions causing new strokes.�

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

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

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

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

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

NAC may also combat the abnormal blood clotting seen in many cases, and helps loosen thick mucus in the lungs. Interestingly, with COVID-19 treatment as a new indication, the U.S. Food and Drug Administration suddenly cracked down on NAC, claiming it is excluded from the definition of a dietary supplement, as 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 fewer than 1,170 NAC-containing products in the National Institutes of Health’s Dietary Supplement Label Database.27

Why the CHOP Study Has Additional Significance

The fact that CHOP researchers are recommending NAC for the treatment of HCCAA is of particular significance because of their historical opposition to the use of dietary supplements. In October 2013, it announced that its list of medications 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 as a matter of policy.28

Their reasoning was that dietary supplements are “essentially unregulated� with “no sound information� about side effects, drug interactions or standard dosing, which they said made giving them to sick children “unethical when the risks are unknown.� But considering the results of the recent study, it would be unethical to withhold such a potentially lifesaving treatment.

The policy is so stringent that parents are asked upon their child’s admission whether they’re taking any supplements. The use of the supplements is then discouraged, including parents being informed of the hospital’s anti-supplement policy and supplement risks, and if “after receiving this information, a parent or guardian insists on continuing to give their child a dietary supplement,� they must sign a waiver to that effect.

Only a limited list of “acceptable products� are allowed in CHOP’s supplement formulary, and it’s unclear if NAC is one of them. If not, it certainly deserves to be added, and perhaps the study will open CHOP’s eyes to the life-saving potential of natural products and dietary supplements.

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