Hello Friends,
Many of you know that I
have been at the forefront of controversy regarding the supplementation of NAC
for Covid-19 after I posted an article on Facebook showing increased risk of adenocarcinoma
with NAC use. The following is a careful and very prayerful examination
of this position. What I found was, in fact, much more of an issue than
increased risk of cancer. Please read and provide feedback if you are able.
Regards,
Ron Meinhardt
founder@healthislife.org
Introduction:
Reports of the efficacy of
the compound N-acetylcysteine in improving Covid-19 outcomes have been
circulating around lately in health and wellness circles. When asked of my own
personal opinion with NAC in supplement form, I replied that I had ceased
taking or recommending its use because of the risk for cancer initiation often
accompanying protein isolate or amino acid supplementation (1,2,3,4). However,
since very recently being challenged on this hypothesis, I have dug deeper into
the voluminous amount of research surrounding this substance. The purpose of
this report is to share some of my findings. If you are currently taking this
as a dietary supplement I strongly encourage you to read this article in its
entirety.
NAC - What is it?
Here’s a little
background info I found surprising… L-cysteine, the main ingredient in
N-Acetylcysteine, has been historically manufactured in foreign countries (in
particular China) from human hair (a potent source of the amino acid). Other
sources may include bird feathers or even synthetic derivation (5). One of the
more popular processes in which L-cysteine is then “acetylated" into NAC
is described as follows: “we have prepared […NAC…] using 1 equiv. of acetic
anhydride [which is basically vinegar without moisture] and a variety of acid
acceptors in aqueous tetrahydrofuran)” (6). Furthermore, undesired byproducts
(from 35-20%) will need to be removed although even higher purity varieties may
contain some degree of contaminants (7).
Therapeutic effects:
There are many
studies showing benefit in vitro (outside the body) and vivo (inside the body),
of the indirect free radical scavenging effects of NAC (8). However as one
researcher wrote: “NAC should not be considered to be a powerful antioxidant in
its own right: its strength is the targeted replenishment of GSH [Glutathione]
in deficient cells and it is likely to be ineffective in cells replete in GSH”
(9).
The role of NAC in the
treatment many diseases is still unclear and controversial. It has been
shown to possess strong mucolytic properties (by breaking the disulfide bonds
in mucus) and is frequently given in cases of acetaminophen overdose to
decrease liver toxicity (10). However, one article, reviewing over one hundred
and three research studies related to the clinical use of this compound, found
that “numerous, mainly small clinical trials with variable doses have yielded
inconsistent results in a wide variety of diseases” (11). Furthermore, some of
the reported benefits of NAC were shown to be due to dosages that would be
difficult to achieve in the clinical setting, in particular with oral
supplementation (12).
Unexpected side effects:
Besides potentially
increasing the risk of cancer (1,2,3,4), NAC has been found to decrease the
cancer-fighting effectiveness of a large class of naturally medicinal
substances, such as curcumin (13), berberine (14), vitamin D (15), melatonin
(16), selenium (17), and cucurbitacin (18). This is due to the fact that these
compounds utilize oxidation (aka production of free radicals) to initiate
cancer cell death (apoptosis) (13,14,15,16,17,18) and the robust and persistent
repletion of glutathione by NAC neutralizes this effect.
This point deserves
further elaboration due to the misconception that antioxidants are usually seen
as “good” and free radicals “bad.” While persistently disarming free radicals
(aka reactive oxygen species or R.O.S.) is a great idea in many disease processes
it can be dangerous in others. In the case of pulmonary disease: “based on this
knowledge, some researchers suggested that a faster clearance of ROS could
reduce lung damage and improve lung function.” (19) However, “ROS generation by
[…] pathogens has also been established in respiratory epithelial cells, and
the modulation of ROS was reported to be important for respiratory
virus–induced innate immune mechanisms” (ibid).
An example of the positive effects
of NAC’s action are the studies showing significant reduction of the severity
of some influenza infections (20, 21, 22). This may be due largely to the fact
that the virus is spread readily through replication (multiplication inside the
cell) and consequent rupture of the cell membrane (apoptosis) (23). According
to one study: “apoptosis induction is an antiviral host response, however,
influenza A virus (IAV) infection promotes host cell death” (ibid). This allows
the virus, after sufficient intercellular replication, to exit the cell in
masse. Apoptosis is triggered by the overwork of the virus-hijacked cell’s
organelles (mitochondria and endoplasmic reticulum) and production of large
amounts of oxidative stress. NAC can suppress these free radicals and reverse
the trend toward apoptosis and subsequent release of virons, thus slowing the
spread of the Influenza virus.
While this process may be
potentially beneficial in influenza infection, it may actually be dangerous in
human coronavirus infection. One reason is that the coronavirus can efficiently
exit the host cell the process of viral budding instead of apoptosis (24). In
fact, cells infected with coronavirus can even adhere and fuse with neighboring
cells “...lead[ing] to the formation of giant, multinucleated cells, which
allows the virus to spread within an infected organism without being detected
or neutralized by virus-specific antibodies” (Ibid). This can lead to
asymptomatic infection but with massive amount of viral shedding, thus potentially
making an infected person apparently healthy but extremely contagious.
During the replication of
coronaviruses "massive amount[s] of structural proteins [are] synthesized
to assembly progeny virions. The production, folding, and modification of these
proteins undoubtedly increase the workload of the ER [endoplasmic reticulum]”
(24).. However, coronaviruses naturally block a critical pathway (the
integrated stress response) that would normally trigger a decrease of viral
replication and apoptosis of the infected cell. This is at least in part by
limiting the secretion of the cell’s red alert compounds known as “interferons”
(Ibid). However, interferon (alpha) production can still occur (leading to
apoptosis) due to the massive amount of oxidative stress generated by viral
production (Ibid). Thus, production of functional interferon
after infection with SARS-CoV-1 is purported to be "essential for the
control of potentially lethal coronavirus infections” (25, 26).
NAC and coronavirus
replication:
Reducing the free
radical generation by stressed organelles with N-acetylsysteine (a potent and
persistent replenisher of intercellular glutathione) has been shown to
potentially encourage an environment supporting enhanced viral replication in
human coronavirus infection (resulting in enhanced endoplasmic reticulum
folding capacity) (27). To make matters worse, NAC may alter the profile of the
normal production of cytokines (chemical messengers mediating the inflammatory
response) (19, 27).
The latter is concerning
seeing that immune dysregulation is already a hallmark of coronavirus
infection. A study in the journal Clinical Infectious Diseases “observed
leukopenia in 47% of patients, lymphopenia in 84%, and T lymphopenia in 95%.
CD4(+) T lymphocyte levels were reduced in 100% of patients, CD8(+) T
lymphocyte levels were reduced in 87%, B lymphocyte levels were reduced in 76%,
and natural killer cell levels were reduced in 55%” (28).
Also of interest, in HIV
infection, dosages of NAC typical of oral administration, but not intravenous,
caused an increase in the infection rate of monocytes (27). After viral
infection these immune cells are themselves at increased risk for aberrant
behavior, potentially letting go of their munitions in the lungs and causing a
devastating condition known as cytokine storm- the single most deadly end
result of Covid-19 infection (29, 30)
Where do we go from
here?
Ultimately we will
need to weigh the evidence ourselves and make an educated decision. The good news
is that we can safely enjoy the benefits of dietary bioavailable
cysteine and thereby ensure healthy normalization of
glutathione levels. For example, raw garlic contains natural forms of this
amino acid, such as S-allyl-cysteine, which also shows potent anti-cancer
effects (31, 32, 33). Furthermore, adequate amounts of vitamin D have been
shown to safely regulate levels of glutathione (34)
By now you may have
developed second thoughts about utilizing N-acetylcysteine, or for that matter,
any substance that has not been adequately tested, against Covid-19. What then
can we rely upon in the face of such an unknown threat?
Here is some timeless
counsel:
“The simpler
remedies are less harmful in proportion to their simplicity; but in very many
cases these are used when not at all necessary. There are simple herbs and
roots that every family may use for themselves and need not call a physician
any sooner than they would call a lawyer.” — 2nd Selected Messages, page
279
“When physicians
understand physiology in its truest sense, their use of drugs will be very much
less, and finally they will cease to use them at all. The physician who depends
upon drug medication in his [practice] shows that he does not understand the
delicate machinery of the human organism.”—Unpublished Testimonies, October 12,
1896.
“Educate away from drugs.
Use them less and less, and depend more upon hygienic agencies; then nature
will respond to God's physicians—pure air, pure water, proper exercise, a clear
conscience.” — The Medical Ministry, page 259
“Pure air, sunlight,
abstemiousness, rest, exercise, proper diet, the use of water, trust in divine
power—these are the true remedies.”—The Ministry of Healing, page 127
In summary:
The concept of
temperance is shown to apply even at the molecular level: moderate use of that
which is good, and complete abstinence of that which is harmful. Normal levels
of intercellular glutathione have a positive effect upon our health, however,
given the raw materials, the body can do a better job of managing the fine line
of production so that the compound not used as a cloak for cancer or viral
development. Let us all seek to become better acquainted with this principle,
for we are entering upon an era in this world’s history that will necessitate
more careful practices than heretofore have characterized our work.
References:
1) JCI Insight. 2019 Oct 3;4(19). pii:
127647. doi: 10.1172/jci.insight.127647.
2) Sci Transl Med. 2014 Jan 29;6(221):221ra15.
doi: 10.1126/scitranslmed.3007653.
3) Rejuvenation Res. 2014 Jun;17(3):306-11. doi:
10.1089/rej.2014.1577.
4) Sci Transl Med. 2015 Oct 7;7(308):308re8.
doi: 10.1126/scitranslmed.aad3740.
5)https://oukosher.org/blog/consumer-kosher/what-could-be-wrong-with-l-cysteine/
6) N-Acylation of Cysteine
Tellis A. Martin, John R. Corrigan, and Coy W. Waller
The Journal of Organic
Chemistry 1965 30 (8), 2839-2840
DOI: 10..1021/jo01019a509
7) https://www..sigmaaldrich.com/catalog/product/sial/a7250?lang=en®ion=US&utm_medium=cpc&utm_source=bing&utm_term=n%20acetyl%20cysteine&utm_campaign=SIAL%20Position%20Support%20Global%20(Bing%20ebizpfs)&utm_content=sial/a7250
8) Oxid Med Cell Longev. 2018; 2018: 2835787.
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28.
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