Sulfites regimen [CRS mailing list thread, Oct 2001]

[KHashmi316]

As I may have reported in prev posts, the vast bulk of my meal is  a raw-veg puree, Vita-Mixed into a texture, viscosity and mouth feel of Cream of Wheat or apple sauce. I usually puree and consume the veggie/water/guar/cellulose mix within about 18 hours, 'fridging the stuff in Tupperware containers. 

Lately, I've readjusted my prep schedule a bit in that the containers with puree meal may sit 36-48 hours. Based on some detected flavor change, there may be some "un-preservation" or degradation going on. I recall, decades ago on the CRS list, some discussion about the use of preservatives. One in particular - -as discovered by Michael Rae -- may have, in fact, been a type of senolytic (my mis-use of that word, not Michael's!).

For a while, I was adding a very little bit of the stuff to various recipes, but discontinued use over 15 years ago. Ditto on non-use of any food or alch. items for about that same amount of time. 

In light of my new meal prep schedule above, I think I'll experiment a bit with some sodium metabisulfite again. Mostly to better preserve the meal in the fridge. 

It's difficult to find info on health benefits of metabisulfite today, so I've copied and pasted some of the Oct 2001 email discussion below. MR did provide extensive Ref notes below his reply, way back when!.The formatting is whacky because of AOL,  so following the text is a bit of chore (apologies!).

==========

Subj: Sulfites "regimen"
Date: 2001-10-05
To: crsociety@lists.uchicago.edu

Michael Rae...

You've recently brought to our attention some of the anti-AGEing properties of sulfites (specifically, sodium metabisulfite). Could you recommend a regimen dosage -- as well as the best time (and/or with which specific foods) to consume it? We only know of your experience with the brownies. How efficacious would sulfite consumption be via foods that normally contain the compound: basalmic vinegar, red wine or the stuff used to preserve dried fruit. Prior to your pro-sulfite post, I specifically chose dried fruit that was UN-sulfered; now it's the opposite. Another thing I not too keen on is an upper limit; at which level do sulfites become toxic?

Any suggestion by you or anyone else on the list are appreciated!

Thanks,
Khurram

KHashmi316@aol.com

In a message dated 2001-10-10 7:24:15 PM Pacific Daylight 
Time, mikalra@cadvision.com writes:

> All:
> 
> KHashmi316@aol.com wrote:
> 
>> You've recently brought to our attention some of the anti-AGEing  properties  of sulfites (specifically, sodium metabisulfite).
>> Prior to your pro-sulfite post, I specifically chose dried fruit that  was UN-sulfered; now it's the opposite. Another thing I not too keen on is an  upper limit; at which level do sulfites become toxic?

> Some safety issues have been brought up. FOR THE PROSECUTION, there is, first, an in-vivo demonstrated toxicity, which appears to 
be realted to  its interactions with PUFA (1,2). These seem to be 
somewhat retarded by > adding in extra antioxidants (which I do to my cooking 
oils anyway: BHT  & CoQ). 

> There also appear to be some issues related to "swamping" 
of sulfite oxidases (3), and a closely-related (& perhaps fully 
causal) inhibition of Mb (5). Depletion of thiamine may somehow be an issue 
(4 -- based on  the title alone, NB), and NO/EDRF also seems to be 
inactivated by  sulfites (6). Further, a study in plants suggests that it 
may inhibit  cellular uptake of Se (7), tho' an in vitro animal study 
(which confirms  the effect) also suggests an upside (8); this may itself 
be linked to the Mb issue (5), & ensuring good intake of both ought to 
ameliorate  concerns re either (5a looks suggestive in this regard, 
based on the title).

> Feeding to rats also upregulated several enzymes, mostly 
digestive (9); the authors note that "The origin of such altered enzyme 
activities is still unknown", & I'd suggest that the health implicatioins are equally nebulous.
> 
> OXIDIZED sulfur radicals from sodium sulfite is mutagenic 
in vitro (11); of course, lots of things are... But when administered in 
drinking water, Japanese researchers found it to PROMOTE stomach 
cancer (15).
> FOR THE DEFENSE: All that said, the FDA says you're fine 
if you don't have an allergy. They've been wrong before, & the food 
industry has a clear interest in keeping the stuff available, but there 
aren't the kinds of markets & profits to defend we see in 
questionable decisions like aspartame; further, they ARE found in foods 
naturally, & HVE been around as an additive for a long, long time.
> 
> Most of the concerns raised above come from in vitro 
studies, or from administering sulfites in drinking water. The best 
toxicity study I could find on the stuff was (10), which administered the 
stuff in vivo, IN FOOD. The fact that they used baked biscuits makes it 
esp valuable for brownies etc, tho' I'd like to know about the PUFA 
content of same.
> "The studies were performed on Sprague Dawley rats for 28 
and 85 days of dietary exposure. Diets were prepared from sulphited or 
untreated (controls) biscuits with the addition of sugar, protein, 
vitamins and minerals according to the nutritional requirements of the 
animals. ...
> [R]ats were administered diets containing sulphited 
biscuits at levels ... corresponding to 10-15, 35-45, 150-170 and 310-340 mg 
SO2/kg diet."
> "[N]o death or clinical abnormalities were reported. 
Growth rate, food consumption and food conversion efficiency were not 
affected by treatment. No dose-related changes were observed for 
haematology, clinical chemistry, ocular examination, renal-function, 
urinalysis, organ weights or gross and microscopic examinations. The 
liver concentrations of vitamins A, B1, C and E were not 
significantly changed> except for an increase in vitamin E in high-dose males 
after 28 days' > exposure."
> 
> "Based on these data, the no-observed-adverse-effect 
level (NOAEL) of sulphites in baked biscuits was judged to be 310 mg 
SO2/kg diet or 25 mg/kg body weight/day."
> 
> In an adult AL human, this would av'g 1750 mg/day; 
HOWEVER, one might have to adjust for metabolic rate based on 
surface-to-volume issues. Per  Steve Harris, via Tom Matthews:
 
>> The standard metabolic animal to human dose scaling rule 
is the -1/4  power of the body weight.>> Since a human weighs about 3000 times what a mouse does, 
this means the scaling factor is about 7.4. Ie. after scaling directly 
by weight, divide mouse dosages by 7.4 to get human dosages.
http://groups.google.com/groups?hl=en&selm=3984399D.81A881C0%40internet.look.
> ca
> 
> ... in which case it MIGHT be much lower. Granted that an 
adult S-D rat weighs in at 300 g, & then based on a 70 kg AL human, the 
dose might be more like 1/3.9 of this, or ~447 mg.
> 
> NB, however, that cancer (eg) is unlikely to show up in 
short-term studies in small cohorts; this is the reason for the high 
doses used to test for in vivo carcinogenicity of pesticides & 
preservatives, which are subsequently (& quite disingenuously (or, in other cases, ignorantly)) mocked by industry mouthpieces ("Why, you'd 
need to swallow a BOXCAR of alar-treated apples to reproduce these doses!").

> Interestingly, high sulfite intake appears to actually 
ENHANCE detoxification of some xenobiotics, via increased sulfate 
conjugation (Phase II): "This was demonstrated using paracetamol as a 
substrate.
> Sulfite was even more efficient in supplying sulfate for 
sulfate conjugation than inorganic sulfate. Sulfite was 
furthermore shown to be protective against the toxicity of both 
N-acetyl-p-benzoquinone imine (NAPQI), the reactive paracetamol metabolite, and 
acrolein, a reactive aldehyde which is a metabolite of allyl alcohol. This 
protection is most likely due to direct reaction between sulfite and these 
reactive  metabolites in a manner similar to that occurring with GSH and other thiols. When NAPQI and acrolein were 
generated  intracellularly in isolated hepatocytes from paracetamol 
and allyl alcohol, respectively, toxicity was also expressed. In 
this case sulfite  only protected against allyl alcohol induced toxicity and 
not against paracetamol induced toxicity" (12).

> Likewise, as one would expect, "The mutagenicity of 
methylglyoxal was  suppressed by sulfite" IN VITRO (13); methylglyoxal is a 
reactive dicarbonyl -- a late-stage AGE precursor, & one of the 
nasties trapped by aminoguanidine, thus confirming the real benefits of 
the the anti-AGE effect of sulfites IN VITRO. IN VIVO, a similar effect 
was seen with aldehydes from cigarrette smoke (16, 16a), prob thru' the 
same action in binding carbonyl groups IMHO; indeed, many such aldehydes 
are, in fact, glycotoxins (ie. environmental AGEs) (17)!

> I would only suggest using the stuff as a cooking aid, to 
reduce food AGE formation, in foods such as baked goods; I do NOT 
reccomend using it as an active drug taken on its own. For food use, the 
guidelines  (non-binding) in Canada are based on the likely intake of 
an "average" person of the food in question, so that a voluntary 200 
mg/kg food is maintained in potatoes, eg, but the absolute max for 
anything is 22.5 times this (2500 mg/kg food).

> & even for this use, what I'm doing is using only a v. 
low dose of Na metabisulfite, sprinkled on the very TOP of the brownies, 
where heat exposure & VISIBLE browning is greatest. This minimizes 
contact w/brownie PUFA. Instead, I mix in relatively high amounts 
of NAC: cysteine was very nearly as potent as metabisulfite in 
the original study (18), and (19) reported potent in vitro inhibition 
of degradation products of glucose by NAC per se as well as bisulfite ( 
in vitro, heating glucose can create reactive dicarbonyls such as 
glyoxal via the Wolff and Namiki pathways (this is how one caramelizes 
pure sugar in the absence of protein); tho' this reaction pathway is likely 
irrelevant in vivo (20), it's a serious source of food AGE).
>
> I throw in a bit of carnosine, too, & taurine: they were 
both pretty mediocre per (18), however, & carnosine is rather 
expensive to use for this purpose (not that I'm SURE that taking it as a 
supplement is justified either: humans have a SPECIFIC carnosinase 
enzyme which rodents lack, so an effective human dose might be MANY 
tmes higher than what's been used in rodent studies -- & we still don't 
have any clear, solid evidence of an in vivo antiglycating effect (but 
see (21), tho' other bennies have certainly been reported).

> To return to Khurram's question,

>> Could you recommend a  regimen dosage -- as well as the best time (and/or with 
which specific foods) to consume it? We only know of your experience with the 
brownies.

> Well, as noted above, I DON'T reccomend using it as you 
seem to be  thinking -- as a dose-format drug for active consumption. 
Taking the  stuff in food which has been processed in a way likely to 
produce  glycotoxins should maximize its benefits while minimizing 
its risks, as  the stuff reacts with nasties & its own potential toxicity is neutralized. I would conservatively suggest keeping 
intake down to below  500 mg in any case -- should be easy on an otherwise 
largely natural,  "unprocessed" diet.

>> How efficacious would sulfite consumption be via foods that normally  contain the  compound: basalmic vinegar, red wine or the stuff used to preserve dried fruit.

> These are good examples of the above principle. As well, such low-dose intake should certainly be safe, based on years of use, & will result in lower food AGE & possible in vivo anti-AGE effects.

 > -Michael

> 1: Til HP, Feron VJ.
> Toxicology of sulphiting agents. I: Animal studies.
> Food Addit Contam. 1992 Sep-Oct;9(5):587-95. Review.
> PMID: 1298664 [PubMed - indexed for MEDLINE]
> 
> 2. Southerland WM, Akogyeram CO, Toghrol F, Sloan L, 
Scherrer R.
> Interaction of bisulfite with unsaturated fatty acids.
> J Toxicol Environ Health. 1982 Sep;10(3):479-91.
> PMID: 7175975
> 
> 4. Bibl Nutr Dieta 1966;8:126-38
> [Thiamine-sulfite antagonism in vivo--an antithiamine 
action].
> [Article in German]
> Cremer HD, Hotzel D.
> PMID: 5917212
> 
> 5. Sardesai VM.
> Molybdenum: an essential trace element.
> Nutr Clin Pract. 1993 Dec;8(6):277-81.
> PMID: 8302261
> 
> 5a. Nutr Rev 1975 Jun;33(6):185-6
> Bisulfite toxicity in molybdenum-deficient rats.
> PMID: 1095971
> 
> 6. Harvey SB, Nelsestuen GL.
> Reaction of nitric oxide and its derivatives with 
sulfites: a possible
> role in
> sulfite toxicity.
> Biochim Biophys Acta. 1995 May 29;1267(1):41-4.
> PMID: 7779867 [PubMed - indexed for MEDLINE]
> 
> 7. Lalitha K, Easwari K.
> Kinetic analysis of 75selenium uptake by mitochondria of 
germinating Vigna
> radiata of different selenium status.
> Biol Trace Elem Res. 1995 Apr;48(1):67-89.
> PMID: 7626374
> 
> 8. Park YC, Whanger PD.
> Toxicity, metabolism and absorption of selenite by 
isolated rat hepatocytes.
> Toxicology. 1995 Jun 26;100(1-3):151-62.
> PMID: 7624872
> 
> 9. Rodriguez Vieytes M, Martinez-Sapina J, Taboada 
Montero C, Lamas
> Aneiros M.
> Effect of sulfite intake on intestinal enzyme activity in 
rats.
> Gastroenterol Clin Biol. 1994;18(4):306-9.
> PMID: 7958644
> 
> 10. Ribera D, Jonker D, Narbonne JF, O'Brien J, Antignac E.
> Absence of adverse effects of sodium metabisulphite in 
manufactured biscuits:
> results of subacute (28-days) and subchronic (85-days) 
feeding studies
> in rats.
> Food Addit Contam. 2001 Feb;18(2):103-14.
> PMID: 11288907
> 
> 11. Pagano DA, Zeiger E, Stark AA.
> Autoxidation and mutagenicity of sodium bisulfite.
> Mutat Res. 1990 Jan;228(1):89-96.
> PMID: 2405261
> 
> 12. Sun YP, Cotgreave I, Lindeke B, Moldeus P.
> The metabolism of sulfite in liver. Stimulation of 
sulfate conjugation and
> effects on paracetamol and allyl alcohol toxicity.
> Biochem Pharmacol. 1989 Dec 1;38(23):4299-305.
> PMID: 2597201 [PubMed - index
> 
> 13. Itami T, Ema M, Kawasaki H, Kanoh S.
> Evaluation of teratogenic potential of sodium sulfite in 
rats.
> Drug Chem Toxicol. 1989 Jun;12(2):123-35.
> PMID: 2598829
> 
> 14. Nagao M, Fujita Y, Sugimura T, Kosuge T.
> Methylglyoxal in beverages and foods: its mutagenicity 
and carcinogenicity.
> IARC Sci Publ. 1986;(70):283-91.
> PMID: 3539787
> 
> 15. Takahashi M, Hasegawa R, Furukawa F, Toyoda K, Sato 
H, Hayashi Y.
> Effects of ethanol, potassium metabisulfite, formaldehyde 
and hydrogen
> peroxide
> on gastric carcinogenesis in rats after initiation with
> N-methyl-N'-nitro-N-nitrosoguanidine.
> Jpn J Cancer Res. 1986 Feb;77(2):118-24.
> PMID: 3082823
> 
> 16. Sprince H.
> Protective action of sulfur compounds against aldehyde 
toxicants of
> cigarette
> smoke.
> Eur J Respir Dis Suppl. 1985;139:102-12.
> PMID: 3862602
> 
> 16a. Sprince H, Parker CM, Smith GG, Gonzales LJ.
> Protective action of ascorbic acid and sulfur compounds 
against acetaldehyde
> toxicity: implications in alcoholism and smoking.
> Agents Actions. 1975 May;5(2):164-73.
> PMID: 1171591
> 
> 17. Cerami C, Founds H, Nicholl I, Mitsuhashi T, Giordano 
D, Vanpatten
> S, Lee A,
> Al-Abed Y, Vlassara H, Bucala R, Cerami A.
> Tobacco smoke is a source of toxic reactive glycation 
products.
> Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13915-20.
> PMID: 9391127
> 
> 18. Lehman TD, Ortwerth BJ.
> Inhibitors of advanced glycation end product-associated 
protein cross-
> linking.
> Biochim Biophys Acta. 2001 Feb 14;1535(2):110-9.
> PMID: 11341999
> 
> 19. akai A, Nakayama M, Numata M, Takesawa S, Nakamoto M.
> Sodium sulfite and N-acetylcysteine: new additives to 
dialysate for
> inhibiting
> formation of glucose degradation products and advanced 
glycation end-
> products.
> Adv Perit Dial. 2001;17:66-70.
> PMID: 11510300
> 
> 20. Khalifah RG, Baynes JW, Hudson BG.
> Amadorins: novel post-Amadori inhibitors of advanced 
glycation reactions.
> Biochem Biophys Res Commun. 1999 Apr 13;257(2):251-8. Review.
> PMID: 10198198
> 
> 21: Hipkiss AR, Brownson C, Carrier MJ.
> Carnosine, the anti-ageing, anti-oxidant dipeptide, may 
react with protein
> carbonyl groups.
> Mech Ageing Dev. 2001 Sep 15;122(13):1431-45.
> PMID: 11470131
> 
> --
> The terror attacks are explained -- but not justified -- 
by terror
> created by US government foreign policy. From the cause, 
discern the cure.
> http://www.wfn.org/2000/10/msg00135.html
> http://www.csmonitor.com/2001/0927/p1s1-wogi.htm
> http://www.public-i.org/excerpts_01_091301.htm

=====

=======

In a message dated 2001-10-04 11:42:37 PM Pacific Daylight 
Time, caminante@codenet.net writes:

> has anyone read anything re balsamic being carcinogenic...

Not specifically. Here is URL to the US Government's HERP 
Index (Human Exposure/Rodent Potency). Basically, an index 
of the potency of carcinogens found in certain foods and the 
environment.

Khurram

http://potency.lbl.gov/herp.html

KHashmi316@aol.com

=======

Subj: Re: [CR] Sulfites "regimen"
Date: 2001-10-12
To: crsociety@lists.uchicago.edu

Michael,

A word of thanks for this superbly researched response to my 
queries! I think I can speak for others in saying that you 
have saved and extended our lives many, many times.

As far as sulfites go, I have increased my basalmic vinegar 
portions and added a few more dry apricots to my "regimen." 
Will try not to go above the 500mg threshold you elucidated. 
As far as cooking, well both Dean and Sherm know how rotten 
I am with their recipes. About the only thing I cook 
nowadays is some meat (lightly boiled) and an occasional 
egg. A fave of mine is chocolate tea: organic green tea bag 
+ organic skim milk nuked for about 2 1/2 min on MEDIUM pwr 
5 and; then I add unsweetend cocoa pwdr and some stevia. The 
AGEs in the milk could stand to be eradicated so I may go to 
the wine store and pick up a packet of sulfites. Speaking of 
wine, I wonder if the sulfites are part of the reason why 
certain dark wines -- consumed in moderation -- have their 
pro-health reputation?

A quick query: Some of the food products say they contain 
NATURAL sulfites (e. g, "Sulfites from grapes"). Is this 
form better/safer than a synthetic form (whatever that is)?

Khurram

[KHashmi316]

Just to add ... perhaps what I'm after is a safe and LE-friendly food preservative -- added to perishables, like plant cells that have much more of their surfaces exposed to the "environment" as opposed to their companion cell walls (the must hate purees!). 

Indeed, MR noted this: 

Quote

, I mix in relatively high amounts 
of NAC: cysteine was very nearly as potent as metabisulfite in 
the original study (18), and (19) reported potent in vitro inhibition 
of degradation products of glucose by NAC per se as well as bisulfite ( 
in vitro, heating glucose can create reactive dicarbonyls such as 
glyoxal via the Wolff and Namiki pathways (this is how one caramelizes 
pure sugar in the absence of protein); tho' this reaction pathway is likely 
irrelevant in vivo (20), it's a serious source of food AGE).
>
> I throw in a bit of carnosine, too, & taurine: 

 

[Dean Pomerleau]

 That thread brings back memories of the good old days. I wonder how Sherm is doing. 

If oxidation on top of your concoction is an issue, you could try argon:

https://www.crsociety.org/topic/18085-has-anyone-seen-bryan-johnsons-project-blueprint/?do=findComment&comment=45932

[KHashmi316]

Thx Dean! Yes, those archs would be handy. Yahoo had them up for quite a while, but their messaging platform also bought the farm.

Yes, when I worked in the food industry, we used inert gas (Nitrogen) to blanket large veg. oil tanks. But the gas only protects the exposed (air) surface of food.

The "salad days" of an over-stuffed fridge with large containers, of chopped greens, wasn't cuttin' it 😉

Most of early-day CR issues were resolved, many years ago, by prepping (pureeing) and consuming within 12-18 hrs.