NAC supplements

[Shezian]

Is it worth taking N-acetyl L-cysteine for general immune system boost, especially during these times? 

[Sibiriak]

I don't have time right now to dig up the studies I've looked at,  but I believe  NAC supplementation for "immune system boost"  is pretty dicey.   NAC is definitely one of those "double-edge sword" antioxidants you need to be careful with.

(I'd also be concerned about regular NAC intake nullifying any attempt at dietary methionine/cysteine moderation.  But I'm not clear on that issue.)

 

[Shezian]

thanks so much, l found it hard to find much information online thats why l thought you guys might know. Don't want to take anything that might be harmful for my health,  so l suppose its best  not take this supplement, until more research is done.  Quercertin on the other hand,  seems to be great for the immune system, and from what l read seems safe enough. Would l be correct in saying that?

[Clinton]

NAC is one of those things that I bought into 6 or 7 years ago because it 'boosted glutathione' and was 'anti-aging'  ;-)   ;-)

Some recommendations include taking several times the amount of NAC that you consume of vitamin C ... at this point you need to realize that BOTH are anti-oxidants.

https://www.steadyhealth.com/topics/using-nac-requiring-additional-vitamin-c-intake

How nasty are anti-oxidants?  Your body (possibly ;-)  )already makes (nearly) what it might need ;-) so why add more??? 

Well we thought for quite a while that adding more was just dandy, but when you realize that people that lift weights or run or swim make progress via hormesis you might ask - perhaps a little stress/damage is a good thing.  It is.  Even at a cellular level - consider glucosamine sulfate ... OMG.

https://pubmed.ncbi.nlm.nih.gov/30469486/?from_term=glucosamine+sulfate+lifespan&from_pos=2

https://pubmed.ncbi.nlm.nih.gov/24714520/?from_term=glucosamine+sulfate+lifespan&from_pos=4

the second link above EXPLICITY states that the lifespan extension of glucosamine was erased when NAC was added to the mouse diet.  Incredible.

BTW you can get plenty of cysteine from whey protein ... if that was your goal.  In fact 2 scoops of whey protein brought the level of glutathione from those that are aged back to youthful levels:

https://examine.com/supplements/whey-protein/

"Glutathione stores can be increased in otherwise healthy persons, with whey protein (in this study, pressurized whey) increasing glutathione by up to 24% in 2 weeks with approximately 2 regular scoops (45g) of protein daily.^[44] This increase is additive with the increase seen with resistance training."

Edited May 21, 2020 by Clinton
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[Clinton]

Read that last sentence again.

"This increase is additive with the increase seen with RESISTANCE TRAINING."

Put down the bottle of NAC and pick up a dumbbell might be the best strategy.

Edited May 21, 2020 by Clinton
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[Shezian]

Great thanks so much for taking the time to respond and clearing up through the research. Cheers

[Clinton]

You're very welcome.

My bottom line on this is that, unfortunately, boosting glutathione w NAC just doesn't increase healthspan or lifespan even if it 'looks good on paper'. 

I personally favour whey protein powder over NAC wrt upregulation of glutathione.

I know that whey contains (from a longevity perspective) prohibitive amounts of methionine, leucine, iso-leucine, tryptophan ... BUT if it helps maintain muscle mass in old age and reduce visceral fat along with boosting glutathione then I am in favour - I use it just like I use everything - it is a tool to achieve my goal, and I like whey because it helps me achieve the crude body composition that I think correlates with health and longevity; even though I know at a cellular level it is upregulating mTOR. 
I suppose that I would not argue that whey protein isn’t a food that you’d eat if you were trying to live to age 116 as a man.  BUT I think visceral fat and sarcopenia are larger and more immediate threats.

Edited May 21, 2020 by Clinton

[Sibiriak]

On 5/21/2020 at 8:00 AM, Shezian said:

  Quercertin on the other hand,  seems to be great for the immune system, and from what l read seems safe enough

Quercetin is another polyphenol that's shown  hormetic bi-phasic dose responses (see post on resveratrol here).  

 

Exogenous antioxidants—Double-edged swords in cellular redox state

Health beneficial effects at physiologic doses versus deleterious effects at high doses

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... recent studies employing cell models have highlighted the prooxidative activity of several polyphenols already known as antioxidants such as quercetin, catechins including epicatechin and epigallocatechin-3-gallate (EGCG) and gallic acid.50–55

For example, at high doses, it has been demonstrated that quercetin (50 µM) can potentiate superoxide radical (O₂^•-) generation within isolated mitochondria and cultured cells.51

In another study, the antioxidant activity of quercetin was observed only at low doses (0.1–20 µM) while higher concentrations (>50 µM) decreased cell survival and viability, thiol content, total antioxidant capacity and activities of SOD, CAT and glutathione S-transferase.52

It has also been demonstrated that flavonoids (quercetin and fisetin) at low concentrations (10–25 µM) protect rat H4IIE cells against H₂O₂-induced cytotoxicity, DNA strand breaks and apoptosis, whereas high concentrations (50–250 µM) caused cytotoxicity, DNA damage and apoptosis.50

It was also shown that flavonoids at high concentrations can generate ROS by autoxidation (e.g., myricetin and quercetin) and redox-cycling (e.g., quercetin).56–59

 

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[...]In general, antioxidants when delivered as dietary supplements contain isolated (synthetic or concentrated) compounds in concentrated form. For example, a typical vegetarian diet contains 20 times less quercetin than a single dose of many supplements of this antioxidant available on the market.53 High, isolated concentrations of carotenoids, EGCG and vitamin C are also common (Table 3). Carotenoid supplements for example mostly contain β-carotene, lycopene or lutein and xeaxanthin, and contain often the manifold of a typical daily intake. Unfortunately, for many dietary antioxidants, no upper tolerable intake level (UL) has been established, with exception for some vitamins.124,125 While carotenoids have been taken also for its vitamin A activity and against macular degeneration,36,126,127 especially lycopene has been marketed as an antioxidant.128 Negative effects of taking high amounts of lycopene, also from diets, have been hypothesized to cause skin alterations and contribute to adverse effects such as abdominal problems (French Food Safety Agency AFFSA, www.afssa.fr/Documents/NUT2004sa0336.pdf).

 

Now,  the levels you might achieve by popping 500mg capsules of isolated quercetin may not reach the  high quercetin levels in the  in vitro studies cited above due to low bioavailability,   but the hormetic principle involved is something worth considering.

Personally, I think that unless you have a specific medical condition you are trying to address (eg. allergies, arthritis),  there is no reason to take quercetin in an  high dose, isolated supplemental form ( it's often quercetin dihydrate,  a rare form derived from the Japanese pagoda tree (Sophora japonica) and not found in most fruits  and vegetables).

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...there is increasing evidence that the observed associated health advantageous effects of plant food consumption may not be attributable to a specific compound, but rather to the whole fruit and vegetable, following additive or synergist actions of complex mixtures of phytochemicals and nutrients.27,106

While earlier epidemiological and observational studies have suggested that increased carotenoid intake can go along with decreased risk of developing certain types of cancer, such as digestive tract cancer,107 or lung cancer108,109 and decreased risk of markers of CVD,100 many individual supplementation trials in humans failed to result in observed health beneficial effects or even suggested that antioxidant compounds can be toxic under certain conditions such as at high doses or when synergistic compounds are lacking.

 

3. Dietary Sources of Quercetin

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Quercetin-type flavonols (primarily as quercetin glycosides), the most abundant of the flavonoid molecules, are widely distributed in plants. They are found in a variety of foods including apples, berries, Brassica vegetables, capers, grapes, onions, shallots, tea, and tomatoes, as well as many seeds, nuts, flowers, barks, and leaves. Quercetin is also found in medicinal botanicals, including Ginkgo biloba, Hypericum perforatum  [St John's wort,], and Sambucus canadensis [ American elder ] [6,7,8].

In red onions, higher concentrations of quercetin occur in the outermost rings and in the part closest to the root, the latter being the part of the plant with the highest concentration [9]. One study found that organically grown tomatoes had 79% more quercetin than chemically grown fruit [10].

Quercetin is present in various kinds of honey from different plant sources [11]. Food-based sources of quercetin include vegetables, fruits, berries, nuts, beverages and other products of plant origin [12]. In the determined food, the highest concentration is 234 mg/100 g of edible portion in capers (raw), the lowest concentration is 2 mg/100 g of edible portion in black or green tea (Camellia sinensis) [13].

Dietary intake of quercetin was different in several countries. The estimated flavonoid intake ranges from 50 to 800 mg/day (quercetin accounts for 75%), mostly depending on the consumption of fruits and vegetables and the intake of tea [14]. In the Suihua area of northern China, quercetin intake was reported to be 4.37 mg/day, where the main food sources of flavonol was apples (7.4%), followed by potatoes (3.9%), lettuce (3.8%) and oranges (3.8%) [15], whereas the average quercetin intake was 4.43 mg/day, with apple (3.7%), potato (2.5%), celery (2.2%), eggplant (2.2%), and actinidia (1.6%) being the main food sources of quercetin in Harbin, China [16]. The most recent study showed that quercetin intake is about 18 mg/day for Chinese healthy young males.

In the USA, flavonol intake is about 13 mg/day for U.S. adults, while quercetin represents three-quarters of this amount. The mean quercetin intake was approximately 14.90 to 16.39 mg per day. Onions, tea, and apples contained high amounts of quercetin [17].

In Japan, the average and median quercetin intakes were 16.2 and 15.5 mg/day, respectively; the quercetin intake by men was lower than that by women; and the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer [18].

In Australia, black and green teas were the dominant sources of quercetin. Other sources included onion, broccoli, apple, grape, and beans [19]. Analysis of the 24-h recall data indicated an average adult intake of total flavonoids (>18 years) of 454 mg/day. Apple was the most important source of quercetin until age 16–18 years, after which onion became an increasingly important prominent source [19].

In Spain, the average daily intake of quercetin is 18.48 mg/day, which is significantly higher than that in the United States (9.75 mg/day), based on sources like tea, citrus fruits and juice, beers and ales, wines, melon, apples, onions, berries and bananas.

 

 

 

Edited May 22, 2020 by Sibiriak

[TomBAvoider]

Again, it's possible to get too much in the way of polyphenols just from food too - and we (of this board) probably take in more than most people. I consume quite a bit of green tea daily, and apples and many other sources of quercetin. Who knows if we're not overdoing it. There probably are not many studies that focus on folks getting as many polyphenols from the diet as we get - the sample would be pretty small, I suspect. So we're flying a bit blind. YMMV.

[Sibiriak]

53 minutes ago, TomBAvoider said:

I consume quite a bit of green tea daily, and apples and many other sources of quercetin. Who knows if we're not overdoing it.

It's possible,  I don't know how abnormal your diet is,  but epidemiological studies don't give any indication of any problems with high fruit/vegetable intake within normal parameters.

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There probably are not many studies that focus on folks getting as many polyphenols from the diet as we get

 I don't go crazy overboard on F/V myself ( I follow something close to V. Longo's longevity diet) , and I certainly wouldn't make getting as many polyphenols as possible a goal.

Edited May 22, 2020 by Sibiriak

[Sibiriak]

Regarding quercetin supplementation as an  "immune system booster",  the evidence is inconsistent, according to this 2016 review at least:

Quercetin, Inflammation and Immunity

 

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In a randomized, double-blinded, placebo-controlled trial, 1002 subjects took 500 or 1000 mg/day quercetin or a placebo for 12 weeks. For the group as a whole, quercetin supplementation had no significant influence on rates of upper respiratory tract infections (URTI) compared to placebo. In a subgroup of subjects age 40 or older who self-rated themselves as physically fit, 1000 mg/day quercetin resulted in a statistically significant reduction in total sick days and symptom severity associated with URTI [72]. Female subjects were supplemented with 500 or 1000 mg/day quercetin or placebo for 12 weeks. While quercetin supplementation significantly increased plasma quercetin levels, it had no influence on measure of immune function [73]. Quercetin (100 mg/day) did not alter exercise-induced changes in several measures of immune function following three days of intense exercise in trained athletes, but it significantly reduced URTI incidence (1 of 20 subjects in active versus 9 of 20 in placebo group) during the two-week post-exercise period [74]. A similar lack of effect on strenuous exercise-induced immune system perturbation was found in subjects who took 1000 mg/day of quercetin for three weeks before, during, and continuing for two weeks after the 160-km Western States Endurance Run. In this study, however, there were no differences in the post-race illness rates between quercetin and placebo groups [75].

There are several studies in humans investigating the correlation of quercetin and its immunomodulatory effects. Quercetin does indeed reduce illness after intensive exercise. Again, under double-blind conditions, Nieman et al. showed that a supplement of 1000 mg of quercetin alone three weeks before, during and two weeks after a three-day period of 3 h of cycling in the winter resulted in a markedly lower incidence of URTI in well-trained subjects in the two weeks after the intensified training, but had no effect on exercise-induced immune dysfunction, inflammation and oxidative stress [76].

The literature is supportive of the anti-pathogenic capacities of quercetin when it is cultured with target cells and a broad spectrum of pathogens including URTI-related rhinoviruses, adenoviruses and coronaviruses. The impact of the co-ingestion of two or more flavonoids increases their bioavailability and the outcomes on immunity. Nieman et al. determined the influence of two weeks of 1000 mg/day quercetin compared with placebo supplementation on exercise performance and skeletal muscle mitochondrial biogenesis in untrained, young adult males. It resulted in significantly reduced post-exercise measures for both inflammation and oxidative stress, with a chronic augmentation of granulocyte oxidative burst activity [77]. When taken together, quercetin showed a successful reduction in the illness rates of exercise-stressed athletes as well as a chronic augmentation of their innate immune function.

Most in vitro research suggests that quercetin possesses anti-inflammation and immunological improvement. However, the results from a double-blinded, placebo-controlled, randomized trial indicated that quercetin supplementation at 500 and 1000 mg/day for 12 weeks significantly increased plasma quercetin levels but had no influence on measures of innate immune function or inflammation in community-dwelling adult females [73].

The main action of quercetin on inflammation and immune function in vivo is summarized in the Table 2.  [see in text]

These results suggest that quercetin exhibited anti-inflammation and immune-enhancement in vitro (cells) and in vivo (animals), however, studies in human did not totally support these results from cells and animals. The effect, in which quercetin acts as an immune booster in humans, needs to be further verified for future broad application.

 

Of course,  12 week studies are not going to tell us anything about  long term effects on health and longevity.

[Shezian]

Great info, thanks so much guys. 

[Paul11]

I'm sure NAC supplements are the best solution. First of all, you can just do proper nutrition. I take various dietary supplements from https://www.nhc.com/brand/plant-therapy as I have had some problems with my body. I set myself a specific schedule and dosage. I feel really good now. As for vitamins a b c d , you can take it without threats, but watch how much you take so as not to get hypervitaminosis. So be careful. I also wanted to point out that these supplements and vitamins are especially useful to take during a pandemic. Good luck and take care of your health:)

Edited December 5, 2020 by Paul11