27 replies to this topic

[OlderThanThou2]

This results of this study are astounding. The lengthening of telomeres is in the order of 1000bp per year, which would be equivalent to about 30 years of life.

 

Association of nutraceutical supplements with longer telomere length

From the study:

 

 

TL (of the whole telomere genome) and TLS (<20th percentile) was estimated in the participants of both groups. Differences in TL and TLS between the NSG and CG are shown in Figs. 2 and ​and3.3. Quartiles of TL and TLS were estimated from raw data for each patient separately. There was a statistically significant difference (P<0.05) in the TL values of the NSG group, compared to the CG, with increased mean quartiles values for the 1st and 2nd quartile (median). TL measurements were 844 and 953 bases higher in the NSG group compared to the CG. Accordingly, there were statistically significant increased values of TLS in the 2nd (median) and 3rd quartile with values of P=0.044 and P=0.033, respectively. A tendency for difference was found for the 1st quartile comparisons (P=0.051).

 

 

The position of NSG and CG in the nomograms produced from TLDP data (13) is shown in Fig. 4. Lines of 1st, 2nd (median) and 3rd quartile of TL vs. age were presented, showing the age decrement. Mean age with 2SD of age and TL with 2SD of both groups were placed onto the diagram. It is clear that the mean TL levels of the NSG are over the line of the median of a healthy population, while the mean TL levels of the CG are under the line of the median of a healthy population. A difference of approximately 1,000 bases was observed.

Check fig.3 to have an idea of the results. It's very consistant across all the 5% intervals.

 

Here are the supplements used for 6 to 12 months:

 

 

 

Materials and reagents

-One capsule of My Health (Lumis Research SA) contains the following: Mix Vitamin (ascorbic acid, vitamin E acetate 50% natural, niacin, vitamin B1, vitamin K2 Mena Q7 0.2%, vitamin B6, β-carotene, vitamin B12 1%), anti-caking agents (microcrystalline cellulose, mono- and diglycerides of fatty acids, magnesium stearate and silica dioxide.

-One drop of vitamin D (Pure D3, Natural Doctor) contains 2,000 IU vitamin D.

-One capsule of Complete D3&K2 Cofactors (Natural Doctor) contains 2,000 IU vitamin D3, 100 µg K2 and 56 mg magnesium.

-Two capsules of Omega 3-6-9 (Lumis Research SA) contain the following: 740 mg fish oil, 740 mg linseed oil, 740 mg borage oil (Borrgo officinalis L.), 200 mg Krill oil, 370 mg alpha linolenic acid, 312,6 mg eicosapentaenoic acid (EPA), 154,2 mg docosa-hexaenoic acid (DHA), 162,8 mg gamma linolenic acid (GLA), 400 mg linoleic acid and 273,8 mg oleic acid.

-Four capsules of My Antioxidant (Lumis Research SA) contain the following: Mix Vitamin (ascorbic acid, calcium ascorbate, ascorbyl palmitate, natural vitamin E acetate 50%, vitamin B3, vitamin B12 1%, β-carotene, vitamin B5, vitamin B6, vitamin B2, vitamin B1, folic acid, vitamin D3 biotin),

-One capsule of My Probiotics (Lumis Research SA) contains the following: Lyophilized kefir grains, Lactobacillus casei (LMG-S27763), Lactobscillus reuteri (LMG S-27759), Bifidobacterium bifidum (B. bifidum; LMG S-27761), Lactobacillus acidophilus (LMG S-27762), inulin, acacia fiber and hydroxypropyl cellulose. One scoop of My Gastro (Lumis Research SA) contains the following: 2,500 mg L-glutamine (Kyowa®) and 500 mg oligo fructose (FOS). One capsule of My Ubiquinol (Q10) (Lumis Research SA) contains 50 mg of ubiquinol.

 

It's unfortunate they didn't test for telomerase and other things.

 

What in these supplements would be able to produce such a big effect. For sure many of the compounds would have a positive effect on telomeres but the results are astounding, so maybe there is some unknown synergy at play.

Would there be side effects from taking so many supplements? Would activating telomerase so much increase the chances of getting cancer? 

 

Also they used supplements from several manufacturers so I take it  that reduces the chances of faked data.

[pamojja]

 

Would there be side effects from taking so many supplements? Would activating telomerase so much increase the chances of getting cancer?

 

I take much more. Side-effects are a very individual thing. Therefore I would recommend to start with each nutient at lowest possible doses, and increase over weeks, months and years. While monitoring regular lab-markers (25-OH-D3 for high dose vitamin D). Better start out without so many combination products. To be able to recognise individual effects, and of course side-effects.

 

In my cases it effected remissions of chronic diseases (PAD, COPD, T2D, ME/CFS..).

[Believer]

It's just a normal vitamin and supplement blend. I don't see why it would produce special effects and effects like these.

[OlderThanThou2]

It's just a normal vitamin and supplement blend. I don't see why it would produce special effects and effects like these.

 

The only  thing that compares I believe is the result that Lizz Parrish got from gene therapy. Who needs gene therapy when you can get that kind of results with supplements? That sounds even less dangerous.

[OlderThanThou2]

I take much more. Side-effects are a very individual thing. Therefore I would recommend to start with each nutient at lowest possible doses, and increase over weeks, months and years. While monitoring regular lab-markers (25-OH-D3 for high dose vitamin D). Better start out without so many combination products. To be able to recognise individual effects, and of course side-effects.

 

In my cases it effected remissions of chronic diseases (PAD, COPD, T2D, ME/CFS..).

 

It's unbelievable what you've been able to achieve. Seriously, you are a warrior!

 

It'd be interesting to know your telomere length and other markers of aging just out of curiosity.

 

The supplements in the study provide 10000-12000IU of vit D. That's indeed a lot, and perhaps it might have had an impact on the high result they got. What I worry the most about is the cancer risk from a very strong telomerase activation over a duration of one year. There are a few minor things like folic acid instead of folate, the vitamin E form they use and other minor things, but it wouldn't be that bad for only one year.

Edited by OlderThanThou2, 13 July 2020 - 08:36 AM.

[pamojja]

I'm sure with so many chronic diseases in remission, my telomeres length seriously shortened, and only little made up by the remissions again. Though at 53 I still have no gray hairs, like a lot of my peers have already.

[OlderThanThou2]

It is hard to say, but with the supplements that you take you might have a good surprise. I saw in the study there is a participant who started with 21000bp and who ended at 23000bp. I would venture to guess he was taking a lot of supplements.

 

Regarding your hair having retained their color, do you drink coffee? Coffee increases H2O2 in the scalp which is said to cause greying. I am 48, I drink coffee and have some grey hair, it might be due to that in part I dont know.

[pamojja]

Yes, every morning I do drink a big mug of filtered coffee. And a lot of sun-shine without needing any suncream protection.

 

 

[OlderThanThou2]

Pretty good, you must have low level of oxidation. And maybe not many senescent cells. Genetics may play a role  as well.

[pamojja]

Pretty good, you must have low level of oxidation. And maybe not many senescent cells. Genetics may play a role as well.

 

Not at all. I do still routinely meassure high levels of oxidation and inflammation. For example liver showed scars from NAFLD, bladder from cystistis, lungs from tubercles, spine from spondilodiscitis - most disapeared now with life-style changes and supplementation (though the by self-healing through calcification fused vertebraes are still visible on the picture of my back above). That's why I take such high doses, obviously they do work in my case to help with worse damage. Before supplementing I got sunburns too. My father had prostata-cancer, my mother just died last year of prostrate cancer (although at 82 only). Also had T2D, high blood-pressure and both hip-bones long ago replaced.

 

[OlderThanThou2]

It's a bit bizarre that you have no grey hair yet if you have oxydation and inflammation. There might be something with your supplements. What do you attribute that to? Personnaly I got most of my grey in short periods when either my diet was bad or I was talking no or few supplements.

[pamojja]

It's a bit bizarre that you have no grey hair yet if you have oxydation and inflammation. There might be something with your supplements. What do you attribute that to? Personnaly I got most of my grey in short periods when either my diet was bad or I was talking no or few supplements.

 

Think you answered your own question. When I got a walking-disability 11 years ago I found myself in a 'nothing left to loose' situation. There wasn't any short periods where either my diet or supplementation was bad since then.
 

Just as with the sun-protection without sun-cream: since there aren't single nutrients to accomplish just that, I must conclude its in synergy (including all life-style changes) which wasn't tested in vivo until now.

 

Therefore I can't attribute those health-benefits to any single one nutrient. Though by amount taken ascorbic acid at 24 g/d for the last 11 years appears to be the major factor. But not without its synergy with all other nutrients and life-style interventions.

 

2nd by amount is only at about 6g: Lysine, Arginines, Glycines, Phytonutrients (all together), Berry and Garlic extracts (assumed 5:1 concentration; if multiplied by 5).

Edited by pamojja, 15 July 2020 - 10:44 AM.

[OlderThanThou2]

It's surely a combination of all the compounds that you take.

 

This being said, I noticed you are taking a huge amount of magnesium (1.5g ). This article mentions magnesium for hair color:

https://www.cesarera...om/en/grey-hair

 

 

 

The following minerals are equally important: Iron (red meat, spinach and fruit), useful for supplying oxygen to the skin and scalp and for the production of pigments that block the insurgence of grey hair, Copper (spinach, crustaceans and potatoes) which collaborates in the synthesis of the melanin that gives color to hair and prevents the insurgence of white hair, Magnesium (vegetables and peanuts) which facilitates the development of enzymes that act both in the production of melanin and hair regrowth, Zinc (meat and fish) which helps the activity of the germinal cells of the matrix and aids hair growth and, lastly, Sulphur (white meat, liver and ham) which contrasts and improves thin and brittle hair.
 

 

Do you still have most of your hair?

 

I don't take a lot of protein to not boost mTOR too much and to not produce too much AGEs, so that may not help for hair color.

[Mind]

I am currently a little suspicious of either:

 

1. The study design - because 1000 bp increase seems unusually large.

 

or

 

2. The telomere theory of aging. If telomere lengthening was "rejuvenating", then we should have noticed a result like this (or similar) a long time ago, since the supplements in the study have been taken by millions of people world-wide for decades.

[OlderThanThou2]

Other scientists should look at their data to make sure there's no error. 

 

I wonder what the probability is, if you measure the LTL of around 20 persons, that one would have 21000bp. Wouldn't that be extraordinarily rare in which case there might be something wrong with their measurements.

 

Maybe another team of scientists should try and reproduce the results they got. And while they're at it measure more parameters.

[pamojja]

It's surely a combination of all the compounds that you take.
 
This being said, I noticed you are taking a huge amount of magnesium (1.5g ). This article mentions magnesium for hair color:
https://www.cesarera...om/en/grey-hair
 
 
Do you still have most of your hair?
 
I don't take a lot of protein to not boost mTOR too much and to not produce too much AGEs, so that may not help for hair color.

 
I'm severely devicient in magnesium, above 2g elemental oral magnesium only alleviated very severe and pain-ful muscle cramps somewhat (1.5 g is only the average intake for 11 years. Finally only almost monthly Mg-sulfate IVs after its 6th ceased muscle-cramps completely.
 
Now almost 3 years later and after my 23rd Mg-sulfate IV, blood levels of Mg are still deficient. But I will get there.
 
All my hair still there. Also protein-levels in serum in my case have always been deficient.

 
The sad thing about ascorbic acid is, though it might be the most studied substance, sadly not at high enough doses. Found actually only one study all these years, which looked at blood markers with 20 g per day intake (now behind a pay-wall): 

 

Journal of the New Zealand Medical Association, 23-August-2002, Vol 115 No 1160

Glycohaemoglobin and ascorbic acid

Copplestone et al1 (http://www.nzma.org....al/115-1157/25/) identified misleading glycohaemoglobin (GHb) results due to a haemoglobin variant (Hb D Punjab) and listed a number of other possible causes for such false results (ie, haemolytic anaemia, uraemia, lead poisoning, alcoholism, high-dose salicylates and hereditary persistence of foetal haemoglobin).

We have observed a significant "false" lowering of GHb in animals and humans supplementing ascorbic acid (AA) at multigram levels. Mice receiving ~7.5 mg/d (equivalent to > 10 g/day in a 70 kg human) exhibited no decrease in plasma glucose, but a 23% reduction in GHb.2 In humans, supplementation of AA for several months did not lower fasting plasma glucose.3,4 We studied 139 consecutive consenting non-diabetic patients in an oncology clinic. The patients had been encouraged as part of their treatment to supplement AA. Self-reported daily intake varied from 0 to 20 g/day. The plasma AA levels ranged from 11.4 to 517 µmol/L and correlated well with the reported intake. Regression analysis of their GHb and plasma AA values showed a statistically significant inverse association (eg, each 30 µmol/L increase in plasma AA concentration resulted in a decrease of 0.1 in GHb).

A 1 g oral dose of AA can raise plasma AA to 130 µmol/L within an hour and such doses at intervals of about two hours throughout the day can maintain ~230 µmol AA/L.5 Similar levels could also be achieved by use of sustained-release AA tablets. This AA concentration would induce an approximate 0.7 depression in GHb. The GHb assay used in our study, affinity chromatography, is not affected by the presence of AA.3 Thus, unlike the case with Hb D Punjab, our results were not caused by analytical method artifact. More likely, the decreased GHb associated with AA supplementation appears related to an in vivo inhibition of glycation by the elevated plasma AA levels, and not a decrease in average plasma glucose.3 If this is true, the effect has implications not only for interpretation of GHb but also for human ageing, in which glycation of proteins plays a prominent role in age-related degenerative changes.

A misleading GHb lowering of the magnitude we observed can be clinically significant. Current recommendations for diabetics suggest that GHb be maintained at 7, a level that is associated with acceptable control and decreased risk of complications; when GHb exceeds 8, re-evaluation of treatment is necessary.6 Moreover, relatively small increases in average blood sugar (ie, GHb) can accompany adverse reproductive effects. A difference in mean maternal GHb of 0.8 was found for women giving birth to infants without or with congenital malformations.7 In either of these circumstances, an underestimation of GHb could obscure the need for more aggressive intervention.

Vitamin usage is common in New Zealand and after multivitamins, AA is the most often consumed supplement.8 Moreover, diabetics are encouraged to supplement antioxidants, including AA. Thus, it seems prudent for primary care health providers to inquire regarding the AA intake of patients, especially diabetics, when using GHb for diagnosis or treatment monitoring.

Cheryl A Krone
Senior Research Scientist
John TA Ely
Director
Applied Research Institute
PO Box 1925
Palmerston North

References:

• Copplestone S, Mackay R, Brennan S. Normal glycated haemoglobin in a patient with poorly controlled diabetes mellitus and haemoglobin D Punjab: implications for assessment of control. NZ Med J 2002;115(1157). URL: http://www.nzma.org....al/115-1157/25/
• Krone CA, Ely JTA. Vitamin C and glycohemoglobin revisited. Clin Chem 2001;47(1):148.
• Davie SJ, Gould BJ, Yudkin JS. Effect of vitamin C on glycosylation of proteins. Diabetes 1992;41(2):167–73.
• Paolisso G, Balbi V, Bolpe C, et al. Metabolic benefits deriving from chronic vitamin C supplementation in aged non-insulin dependent diabetics. J Am Coll Nutr 1995; 14(4):387–392.
• Lewin S. Vitamin C: Its Molecular Biology and Medical Potential. New York: Academic Press; 1976.
• Kenealey T, Braatvedt G, Scragg R. Screening for type 2 diabetes in non-pregnant adults in New Zealand: practice recommendations. NZ Med J 2002;115(1152):194–6.
• Rosenn B, Miodovnik M, Dignan PS, et al. Minor congenital malformation in infants of insulin-dependent diabetic women: association with poor glycemic control. Obstet Gynecol 1990;76:745–9.
• Allen T, Thomson WM, Emmerton LM, Poulton R. Nutritional supplement use among 26-year-olds. N Z Med J 2000;113(1113):274–7.

 

Did you mention the whooping 1% reduction of glycated hemoglobin with 20 g/d intake? - What would have been the results if also other markers of inflammation and oxidation woould have been meassured?

[pamojja]

If telomere lengthening was "rejuvenating", then we should have noticed a result like this (or similar) a long time ago, since the supplements in the study have been taken by millions of people world-wide for decades.

 

I think only people with severely debilitating chronic diseases would consequently take so many supplements consistently. And in which case only making partially up for already through chronic disease processes lost telomere-length. Still dying earlier due to the chronic diseases.

 

I highly doubt that millions of healthy subjects would take so much consitently. Therefore couldn't be noticed.

 

Just the higher mortality in suplement users, due to confounding with serious chronic diseases.
 

[OlderThanThou2]

 
I'm severely devicient in magnesium, above 2g elemental oral magnesium only alleviated very severe and pain-ful muscle cramps somewhat (1.5 g is only the average intake for 11 years. Finally only almost monthly Mg-sulfate IVs after its 6th ceased muscle-cramps completely.
 
Now almost 3 years later and after my 23rd Mg-sulfate IV, blood levels of Mg are still deficient. But I will get there.
 
All my hair still there. Also protein-levels in serum in my case have always been deficient.

 
The sad thing about ascorbic acid is, though it might be the most studied substance, sadly not at high enough doses. Found actually only one study all these years, which looked at blood markers with 20 g per day intake (now behind a pay-wall): 

 

 

Did you mention the whooping 1% reduction of glycated hemoglobin with 20 g/d intake? - What would have been the results if also other markers of inflammation and oxidation woould have been meassured?

 

 

Don't you get stomach upset at 20g/day from too much acidity? Personaly I can't handle more than 1-2g AA ( I had a bad gastritis last year ), to which I add about 1.5g of buffered C. 

 

At what dose does AA become pro-oxidant? I imagine that would depend on the amount of other anti-oxidants one takes.

 

Regarding Vitamin C ability to lower AGEs:

https://www.research...mental_diabetes

 

 

The purpose of this study was to investigate the vitamin C influence on glucose fructosamine and malonylodialdehyde (MDA) concentration in animals with streptozotocin induced experimental diabetes. MDA, glucose and fructosamine concentration were assessed in blood samples. Fructosamine concentration in diabetic animals receiving vitamin C was significantly lower than in group without vitamin C supplementation. MDA concentration in diabetic animals without supplementation was significantly higher than in control groups. MDA concentration in diabetic animals receiving vitamin C was not significantly different from the control group. Conclusions: Supplementation with vit. C had positive effect on protein and lipid peroxydation in diabetic animals. These results can suggest that vit. C plays role in antioxidative system repair and therefore vit. C supplementation can have positive effect in treatment of diabetes.

 

 

 

https://www.scienced...955286396001283

 

In vitro glycation was studied with bovine albumin as the model protein. A mixture of 25 mM glucose/fructose was used as the glycating agent. The Amadori product was quantitated by thiobarbituric acid colorimetry after hydrolysis. Advanced glycation end products were measured by their intrinsic fluorescence. A number of vitamins and nutrients were found to be potent inhibitors of both the glycation reaction and the subsequent end products. The nutrients were effective at physiological concentrations and exhibited dose-response relationships. The inhibitors included ascorbic acid, tocopherol, pyridoxal, niacinamide, sodium selenite, selenium yeast, and carnosine. A significant correlation was found between the inhibition of glycation and the inhibition of AGE formation (P < 0.001). One of the nutrients, ascorbic acid, was used in a pilot study. Eighteen normal subjects, 7 college age and 10 middle age, were supplemented with 1,000 mg of ascorbic acid in the form of Re-Natured Vitamin C® for a period of 4 weeks. Serum protein glycation was decreased an average of 46.8% (P < 0.01). These results underline the importance of nutrition in diabetes and indicate the possibility of therapeutic use of these nutrients for the prevention of diabetic complications.

 

 

1000mg of Re-Natured Vitamin C seem to have been effective. About Re-Natured  technology:

https://www.grownbyn...grown-by-nature

 

The question I wonder about though is that if one wants to counter glycation he needs really large dosages of anti-oxidants, wouldn't that create an anti-oxidative stress?

[pamojja]

Don't you get stomach upset at 20g/day from too much acidity? Personaly I can't handle more than 1-2g AA ( I had a bad gastritis last year ), to which I add about 1.5g of buffered C. 

 

At what dose does AA become pro-oxidant? I imagine that would depend on the amount of other anti-oxidants one takes...

 

The question I wonder about though is that if one wants to counter glycation he needs really large dosages of anti-oxidants, wouldn't that create an anti-oxidative stress?

 

Tolerance and beneficial health benefits of ascorbic acid is overall condition-dependend. In my case with hay fever I easily tolerate up to 50g per day: http://www.doctoryou.../titration.html And goes up exorbitant with just an additional cold.

 TABLE I - USUAL BOWEL TOLERANCE DOSES 
 
                               GRAMS ASCORBIC ACID      NUMBER OF DOSES      
CONDITION                  PER 24 HOURS           PER 24 HOURS 
normal                       4 -  15              4 -  6 
mild cold                   30 -  60              6 - 10 
severe cold                 60 - 100+             8 - 15 
influenza                  100 - 150              8 - 20 
ECHO, coxsackievirus       100 - 150              8 - 20 
mononucleosis              150 - 200+            12 - 25 
viral pneumonia            100 - 200+            12 - 25 
hay fever, asthma           15 -  50              4 -  8 
environmental and                                        
 food allergy              0.5 -  50              4 -  8 
burn, injury, surgery       25 - 150+             6 - 20 
anxiety, exercise and                                    
 other mild stresses        15 -  25              4 -  6 
cancer                      15 - 100              4 - 15 
ankylosing spondylitis      15 - 100              4 - 15 
Reiter's syndrome           15 -  60              4 - 10 
acute anterior uveitis      30 - 100              4 - 15 
rheumatoid arthritis        15 - 100              4 - 15 
bacterial infections        30 - 200+            10 - 25 
infectious hepatitis        30 - 100              6 - 15 
candidiasis                 15 - 200+             6 - 25

With difficulties with acididy, one can always add up to half the weight in sodium bicarbonate to AA in water. Which thereby turns into pH neutral sodium ascorbate. Though stomach acid itself is many times more acidic.

 

Never heard of pro-oxidant effects from oral, but by IV to cancer-cells only. And then there is always the self-limiting intake by bowel-tolerance, which causes flushing of the bowels once one exceeds the exact dose needed.

 

The 46.8% reduction with only 1 g of AA means relative reduction, in-vitro only, and not an absolute reduction in-vivo as with 20 g. LPI didn't find evidence that there is any much better bioavailable form than AA: https://lpi.oregonst...plemental-forms

 

Therefore the needs of ascorbic acid can be highly individual. As already Linus Pauling found many years ago in his book: 'How to live longer and feel better.' Which he termed 'bio-chemical individuality'. A very few might really get enough by dietary intake, others might need much higher amounts.

 

An other historical example where too much isn't too much:

 

 

http://orthomolecular.org/library/jom/2005/pdf/2005-v20n04-p230.pdf

 

Another was Albert Szent-Gyorgyi. In a 1982 letter,14 Stone tells Szent-Gyorgyi of a friend of his who, was diagnosed with prostate cancer at age 44 and then treated with surgery and radiation. A few years later, the cancer had metastasized to the pelvic bone and the patient was declared terminal and given about a year to live. However, Stone writes:

“Since he began taking 80 grams a day in 1979, his well-being has been excellent. He says he feels great most of the time, has also been able to continue working every day and lives a fairly normal life of the years since November 1978 when orthodox medicine said he would be dead. Visually he looks more like an athlete than a terminal cancer patient...

In the last few weeks he has been able to improve his well-being by increasing his ascorbate intake to 130 to 150 grams per day! He has been taking oral doses every hour of 5 to 10 grams of a mixture of nine parts sodium ascorbate plus one part ascorbic acid dissolved in water. These doses are well tolerated and within “bowel tolerance” and he has had no trouble from diarrhea except just lately when he had to reduce the 150 grams a day to 130 grams.

I believe his case is a classic and a good demonstration that if sufficient ascorbate is given to fully counteract all the incident stresses, then the cancer can be controlled. If given early enough in this disease, then cancer may no longer be a problem. Up to now we just haven’t realized how big these daily controlling doses have to be.”

Stone adds that the man’s doctor “ran some ascorbate determinations on Joe’s blood and came up with the highest blood levels I ever saw. At one point it was 35 mg%! Our so-called “normal” but scorbutic population averages 1 mg% or less, our kidney threshold is 1.4 mg%...

I would like to see a crash ascorbate program started on terminal cancer patients using doses in the ranges found to keep his cancer under control. Since these “terminals” have been abandoned by orthodox medicine, they have nothing to lose but their ill health.”

 

The usual reference range for plasma ascorbic acid is 0.4-2.0 mg/dL, which is about 22.7-113.6 µmol/L. While the majority of the population is even below 1 mg/dl, 20g-per-day-dosers in the New-Zealand study had up to 9.1 mg/dl. In this anecdotal example serum levels of even up to 35 mg/dl or 15380 µmol/L were possible, with only good effects in severe disease.

 

One reason why there really might be no real static saturation level in plasma serum-levels might be, the much higher concentrations in all other tissues readily soaking it up: Table 9.312 Human tissue & fluid ascorbic acid concentrations1 (Attribution 4.0 International)

Organ/Tissue | Vitamin C Concentration*

Pituitary Gland           40-50    
Adrenal Gland             30-40    
Eye Lens                  25-31    
Liver                     10-16    
Brain                     13-15    
Pancreas                  10-15    
Spleen                    10-15    
Kidneys                    5-15     
Lungs                        7
Skeletal Muscle            3-4
Testes                       3
Thyroid                      2
Cerebrospinal Fluid          3.8
Plasma                   0.4-1
Saliva                   0.1-9.1

* mg/100 g wet tissue, mg/100 mL fluids

If such astronomically high levels as even 50 mg/dl in the pituary gland with normal serum levels don't fry the pituary by 'anti-oxidant stress', I don't think there is any reason to worry.
 

Edited by pamojja, 16 July 2020 - 10:07 AM.

[pamojja]

Also anti-oxidant function isn't really the major of AA, and a gross simplification of the multy-facetious properties of Vitamin C. Impossible to replicate with any other anti-oxidant. From text-books:
 

• Collagen synthesis. Vitamin C is an essential coenzyme in collagen synthesis. Cofactor in the hydroxylation of lysine and proline, stimulation of gene-expression in fibroblasts; development, maturation and repair of connective tissue such as skin, bone, tendons ligaments, scar tissue, blood vessels and cartilage (anti-scurvy effect = ascorbic). Lack of ascorbic acid results in poorly formed connective tissue in the skin, joints, muscles, and bones.
• Hormone production. Glucocorticoids synthesis in adrenal cortex (stress-response), and Vitamin D-hormone (calcitriol synthesis). Production of epinephrine and norepinephrine, (the hormones released by the adrenal gland in response to stress) are dependent on adequate vitamin C status.
• Neurotransmitter metabolism. Ascorbic acid is essential for the production of norepinephrine and serotonin, two important neurotransmitters in the brain. Conversion of tryptophan in 5-hydrotryptophan (=precursor of serotonin), hydroxylation of dopamine into noradrenalin, synthesis of L-dopa.
• Amidation of neuro-endocrinic hormones. Gastrin, CRH (corticotropin-releasing- hormone and TRH (tyreotropin-releasing-hormone).
• Bile acid synthesis and cholesterol breakdown and excretion. The first key step in the degradation of cholesterol (also tyrosine; bile-acid-synthesis, cholesterol-7-hydroxylasis, HMG-CoA-recductasis) depends on vitamin C. Cholesterol levels in the liver and blood increase if vitamin C status is impaired.
• Carnitine synthesis. Ascorbic acid - together with cofactors niacin, vitamin B6, lysine and methione - is essential for the formation of carnitine, an amino acid required for breakdown of fats for energy. Lack of ascorbic acid lowers levels of carnitine and reduces energy production, producing fatigue and muscle weakness.
• Tyrosine metabolism. Synthesis and catabolism.
• Iron absorbtion and metabolism. Vitamin C sharply increases non-heme iron absorption from diet or supplements. Raising iron transference from transferritin (transport protein) to ferritin (storage protein)-
• Folic acid activation. To tetrahydrofolate (THF).
• Antioxidant function. Vitamin C is the body’s primary water-soluble antioxidant. It is present in the blood, body fluids, and inside all cells and helps protect against oxidative damage by free radicals of lipids (lipid-peroxidation), proteins, nucleic acid and cell membranes. (anti-inflammatory and anti-degenerative effects, e.g. in cancers, diabetes, arthritis, cataracts and cardiovascular diseases..). Vitamin C is also important in the conversion (reduction) of iron and copper to the form in which they function as cofactors in many enzyme systems, such as reduced copper in superoxide dismutase (another antioxidant).
• Antioxidant regeneration. Central building-block in the redox-chain of vitamin C, vitamin E, coenzym Q10 and lipoic acid and/or glutathione, Regeneration of glutathion-disulfide into glutathione.
• Vitamin E sparing effect. Regeneration of tocopherol radicals (vitamin E radical) into the reduced, anti-oxidative active alpha-tocopherol (vitamin E).
• Protection of folate and vitamin E from oxidation. Ascorbic acid protects folate and vitamin E from oxidation and helps maintain these vitamins in their active forms.
• Endothelial cell protection. Raising of NO-bioavailability. (anti thrombotic and blood-lowering effect)
• Detoxification and excretion of drugs and chemicals. Ascorbic acid helps maintain the enzyme systems in the liver that detoxify and excrete drugs and toxic environmental chemicals (such as pesticides and heavy metals). Detoxification of xenobiotika (synthesis/anti-oxidative protection of CYP 450) in the liver, excretion of toxins.
• Antiviral and antibacterial effect. Vitamin C is important for healthy immune function. It is essential for optimum activity of white blood cells and production of the chemical mediators that direct the immune response. Lack of vitamin C sharply increases vulnerability to infection (Immunocompetence). Stimulation of the cellular (antibodies) and hormonal immune system (interferon), protection of phagocytic membranes from oxidative self-destruction (prolonged function-time of immune cells), activation of complementary systems and of chemotaxis.
• Anti-glycation. Inhibition of protein glycosylation and AGE-formation. (e.g. HbA1C).
• Anti-allergic. Vitamin C plays a role in controlling body and blood histamine levels (histamine degradation and mast cell stabilization), and blood histamine levels increase when vitamin C status is poor. High levels of histamine can aggravate allergies, asthma, stomach ulcers, and certain psychiatric disorders.
• Anti-carcinogenic. Inhibition of the formation of carcinogenic nitrosamines from nitrites and secondary amins (especially of the digestive system), protection of DNA from oxidative damage.

 

For example the recommendation by Linus Pauling of 6 to 18 of vitamin C agains cardiovascular disease is mainly because of vitamin C's function to maintain and repair collagen. Especially at the side of arteriosclerosis at the endothelium of the arteries.

Edited by pamojja, 16 July 2020 - 10:34 AM.

[OlderThanThou2]

Tolerance and beneficial health benefits of ascorbic acid is overall condition-dependend. In my case with hay fever I easily tolerate up to 50g per day: http://www.doctoryou.../titration.html And goes up exorbitant with just an additional cold.

 TABLE I - USUAL BOWEL TOLERANCE DOSES 
 
                               GRAMS ASCORBIC ACID      NUMBER OF DOSES      
CONDITION                  PER 24 HOURS           PER 24 HOURS 
normal                       4 -  15              4 -  6 
mild cold                   30 -  60              6 - 10 
severe cold                 60 - 100+             8 - 15 
influenza                  100 - 150              8 - 20 
ECHO, coxsackievirus       100 - 150              8 - 20 
mononucleosis              150 - 200+            12 - 25 
viral pneumonia            100 - 200+            12 - 25 
hay fever, asthma           15 -  50              4 -  8 
environmental and                                        
 food allergy              0.5 -  50              4 -  8 
burn, injury, surgery       25 - 150+             6 - 20 
anxiety, exercise and                                    
 other mild stresses        15 -  25              4 -  6 
cancer                      15 - 100              4 - 15 
ankylosing spondylitis      15 - 100              4 - 15 
Reiter's syndrome           15 -  60              4 - 10 
acute anterior uveitis      30 - 100              4 - 15 
rheumatoid arthritis        15 - 100              4 - 15 
bacterial infections        30 - 200+            10 - 25 
infectious hepatitis        30 - 100              6 - 15 
candidiasis                 15 - 200+             6 - 25

With difficulties with acididy, one can always add up to half the weight in sodium bicarbonate to AA in water. Which thereby turns into pH neutral sodium ascorbate. Though stomach acid itself is many times more acidic.

[/quote]

 

This makes me wonder if older individuals wouldnt need a lot more vitamin C, since they have more inlammation.

 

Never heard of pro-oxidant effects from oral, but by IV to cancer-cells only. And then there is always the self-limiting intake by bowel-tolerance, which causes flushing of the bowels once one exceeds the exact dose needed.

 

I was talking about cases of people who take lots of different types of anti-oxidants, which would decrease the amount of vit C used to neutralize free radicals.

 

The 46.8% reduction with only 1 g of AA means relative reduction, in-vitro only, and not an absolute reduction in-vivo as with 20 g. LPI didn't find evidence that there is any much better bioavailable form than AA: https://lpi.oregonst...plemental-forms

 

 

From reading the website on renatured vit. C it seems it is not just a mix of flavonoids and vit C. They found a way to use the vit C receptors of certain foods to carry more vit C, rendering it more bioavailable. The link 8 in your article shows that natural forms  are better absorbed.

 

https://pubmed.ncbi....ih.gov/3414575/

 

Also in the quote from the study I gave in my previous post, they were talking about 2 studies, one in vitro, one in vivo. The one thats in vivo showed a reduction of 46.8% with 1g of renatured vit C. 

 

 

 

Therefore the needs of ascorbic acid can be highly individual. As already Linus Pauling found many years ago in his book: 'How to live longer and feel better.' Which he termed 'bio-chemical individuality'. A very few might really get enough by dietary intake, others might need much higher amounts.

 

An other historical example where too much isn't too much:

 

 

The usual reference range for plasma ascorbic acid is 0.4-2.0 mg/dL, which is about 22.7-113.6 µmol/L. While the majority of the population is even below 1 mg/dl, 20g-per-day-dosers in the New-Zealand study had up to 9.1 mg/dl. In this anecdotal example serum levels of even up to 35 mg/dl or 15380 µmol/L were possible, with only good effects in severe disease.

 

One reason why there really might be no real static saturation level in plasma serum-levels might be, the much higher concentrations in all other tissues readily soaking it up: Table 9.312 Human tissue & fluid ascorbic acid concentrations1 (Attribution 4.0 International)

Organ/Tissue | Vitamin C Concentration*

Pituitary Gland           40-50    
Adrenal Gland             30-40    
Eye Lens                  25-31    
Liver                     10-16    
Brain                     13-15    
Pancreas                  10-15    
Spleen                    10-15    
Kidneys                    5-15     
Lungs                        7
Skeletal Muscle            3-4
Testes                       3
Thyroid                      2
Cerebrospinal Fluid          3.8
Plasma                   0.4-1
Saliva                   0.1-9.1

* mg/100 g wet tissue, mg/100 mL fluids

If such astronomically high levels as even 50 mg/dl in the pituary gland with normal serum levels don't fry the pituary by 'anti-oxidant stress', I don't think there is any reason to worry.

Mmh you may have a point here. If our ancesters were making vit. C I wonder if those concentration were even higher at that time. 

 

 

[OlderThanThou2]

Also anti-oxidant function isn't really the major of AA, and a gross simplification of the multy-facetious properties of Vitamin C. Impossible to replicate with any other anti-oxidant. From text-books:
 

 

For example the recommendation by Linus Pauling of 6 to 18 of vitamin C agains cardiovascular disease is mainly because of vitamin C's function to maintain and repair collagen. Especially at the side of arteriosclerosis at the endothelium of the arteries.

 

I wonder if it was not a big change for our bodies when our ancestors lost the ability to make vit C, considering the number of things it does in the body. That would have been a lot of things to adapt to at the same time. Maybe we got a mutation that made us better at recycling vit C, I dont know if scientists have theories about that.

 

From the link you posted before, it seems Linus Pauling was not afraid of antioxidants,since he was also advising vit E, vit A and minerals that have antioxidant capabilities. Considering that he knew a thing or two about chemistry, maybe there's not too much risk of going overboard.

Edited by OlderThanThou2, 16 July 2020 - 04:32 PM.

[OlderThanThou2]

For the study about the 46.8% reduced glycation, you can go to:

https://www.research...s_and_nutrients

 

and click on download pdf.

 

 

Supplementation

 

Vitamin C was chosen for a supplementation study since it is a very inexpensive and non-toxic nutrient. Re-Natured Vitamin C@ was used for supplementation because it has been found to be more bioavailable to animals and humans than ascorbic acid alone.L2313 The supplementation produced a significant decrease in serum protein glycation of both the college age and middle age groups, P < 0.05 by a paired t test (Table 2). Five of the 7 college students and all 11 of the middle-age subjects experienced a decline in glycation as a result of the Vitamin C regimen.

 

[pamojja]

2.. it seems Linus Pauling was not afraid of antioxidants,since he was also advising vit E, vit A and minerals that have antioxidant capabilities. Considering that he knew a thing or two about chemistry, maybe there's not too much risk of going overboard.

 

Certainy not with vitamin C, where individual bowel-tolerance is self-limiting from too much than needed intake. With fat-solubles and therefore accumulating vitamin D3 and A I would certainly always monitor blood-levels and know their risks.

 

They found a way to use the vit C receptors of certain foods to carry more vit C, rendering it more bioavailable. The link 8 in your article shows that natural forms  are better absorbed.

 

Fine, if only taking 500 mgs per day. Taking 20 g/d, one bottle of Vitamin-C-Bioflavonoids-Re-Natured at $84.95 would not even last me 2 days.

 

Bought locally, a 100g bottle of pure ascorbic acid costs me € 1.95 and lasts 4 days. Even if the 35% increase in AUC would hold true at higher doses, obviously only sustainable with becoming a millionaire first.

 

Same with liposomal, which only showed a 50% increase in AUC of intracellular levels: https://isom.ca/arti...hydrocortisone/

 

For the study about the 46.8% reduced glycation, you can go to:

 

and click on download pdf.

 

Actually did before posting, still missed the reduction in absolute percentage. Edit: was a different pdf version of this study without tables. Really seems an absolute reduction.


 

 

Edited by pamojja, 16 July 2020 - 04:53 PM.

[OlderThanThou2]

 

Certainy not with vitamin C, where individual bowel-tolerance is self-limiting from too much than needed intake. With fat-solubles and therefore accumulating vitamin D3 and A I would certainly always monitor blood-levels and know their risks.

 

 

There is such a thing as antioxidative stress though:

https://en.wikipedia...xidative_stress

 

https://www.hindawi....cl/2012/480895/

 

There is talk about a 20g daily dose. The prooxidative effect seem to depend on the metals in the body, especialy iron.

 

Also more antioxidants will lead to a decrease of endogenous antioxidants, so that may reduce the chances of a antioxidative effect.

 

But what happens when someone takes supplements that boost endogenous antioxidants at the same time as talking lots of vit C, A, E... In  that case that may become too much, that's what I worry about.

 

Regarding getting a high level of AA, maybe it would be possible to use it with ALA since recycles it, rather than using very high dosages of AA which become less and less absorbed. A 100g powder bag costs around $20. At 600mg per day, it comes down to 12 cents per day. And ALA has other benefits.

[pamojja]

Regarding getting a high level of AA, maybe it would be possible to use it with ALA since recycles it, rather than using very high dosages of AA which become less and less absorbed. A 100g powder bag costs around $20. At 600mg per day, it comes down to 12 cents per day. And ALA has other benefits.

 
In my case the more than neccesary intake of AA is mainly driven by my seasonal rhinitis, where it works by the teaspoonful like any other anti-histamine, but without their side-effects. No other nutrient or combination does that for me. It provides immatiate relieve from sneezing-fits.
 
The most known effect found with too many antioxidants, is decreased strength-gain from exercising. Started to excercise swimming in 2013 on yearly vacations to a South-Indian beach. Only 3 years ago with the remission from walking-disabilty my swiming distance improved from ~40 minutes the preceeding 4 years. This February got to ~80 minutes swimming in the open ocean.
 

But what happens when someone takes supplements that boost endogenous antioxidants at the same time as talking lots of vit C, A, E... In that case that may become too much, that's what I worry about.

That's why I'm regularly testing for inflammation and oxidation, as well as metal status and really every test I can get or affort. Also take all recyclers of endogenous antioxidants, like for example for glutathione described in this article: https://drknews.com/...immune-disease/
 

https://drknews.com/...immune-disease/

... Boosting glutathione levels though a liposomal cream or intravenously—as glutathione taken orally is ineffective—is a key strategy in combating the damage of stress. However these levels can be quickly depleted if the body cannot recycle glutathione to keep the supply on hand to meet the many stressors.

... Glutathione recycling is a separate function from just boosting glutathione levels through a liposomal cream, intravenously, a nebulizer, a suppository, or other means. These forms of glutathione delivery will help one’s antioxidant status but they do not raise levels of glutathione inside the cells. ..

... Supporting glutathione recycling

So how do we support glutathione recycling? The first thing is to reduce the stressors depleting this vital system. The bulk of my thyroid book is devoted to this: balancing blood sugar, addressing food intolerances, restoring gut health, and managing adrenal function are foundational.

Other considerations are neurotransmitter imbalances and hormonal imbalances, which may require specialized guidance from a qualified health care practitioner. And of course making any lifestyle changes you can, such as getting enough sleep, paring down an overactive schedule, making exercise a priority each day, creating time to do things you love, and so on.

Once you have addressed these factors (which for many people can actually take care of the problem) and autoimmune dysfunction persists, then boosting glutathione recycling may be necessary. Below I cover the basic botanicals and nutritional compounds researchers have found support glutathione recycling pathways.

• N-acetyl-cysteine (NAC): NAC is a key compound to glutathione activity. It is rapidly metabolized into intracellular glutathione.
• Alpha-lipoic acid (ALA): ALA directly recycles and extends the metabolic life spans of vitamin C, glutathione, and coenzyme Q10, and it indirectly renews vitamin E, all of which are necessary for glutathione recycling.
• L-glutamine: Research has shown that l-glutamine is important for the generation of glutathione. It is transported into the cell, converted to glutamate, and readily available to intracellular glutathione synthesis.
• Selenium: Selenium is a trace element nutrient that serves as the essential cofactor for the enzyme glutathione peroxidase, which converts GSH to GSSG so glutathione can “take the hit” by free radicals to spare cells.
• Cordyceps: Cordyceps has been shown to activate both glutathione and peroxidase synthesis in the body. It has also been shown to protect cells by engaging the glutathione enzyme cycle.
• Gotu kola (Centella Asiatica): Research has clearly demonstrated that oral intake of gotu kola rapidly and dramatically increases the activity and amount of glutathione peroxidase and the quantity of glutathione.
• Milk thistle (Silybum marianum): Milk thistle has been shown to significantly increase glutathione, increase superoxide dismutase (another powerful antioxidant) activity, and positively influence the ratios of reduced and oxidized glutathione.

Taken together these botanicals and compounds activate the glutathione peroxidase and reductase enzymes that promote a healthy glutathione recycling system.

 

Get to know your blood-results, and supplement accordingly.

 

For example tested Glutathion peroxidase 3 times in 2012, '15 and '17: It rose from non-optimal 43 to 65, and with the last test finally optimal at 72 U/gHb (normal: 27.5 - 73.6; functional medicine optimal: 69 - 90).

Edited by pamojja, 17 July 2020 - 11:32 AM.

[OlderThanThou2]

 

 

In my case the more than neccesary intake of AA is mainly driven by my seasonal rhinitis, where it works by the teaspoonful like any other anti-histamine, but without their side-effects. No other nutrient or combination does that for me. It provides immatiate relieve from sneezing-fits.
 
The most known effect found with too many antioxidants, is decreased strength-gain from exercising. Started to excercise swimming in 2013 on yearly vacations to a South-Indian beach. Only 3 years ago with the remission from walking-disabilty my swiming distance improved from ~40 minutes the preceeding 4 years. This February got to ~80 minutes swimming in the open ocean.
 

Gee when you tell that to your dotor his jaw must be dropping! That's amazing.

 

 

 

That's why I'm regularly testing for inflammation and oxidation, as well as metal status and really every test I can get or affort. Also take all recyclers of endogenous antioxidants, like for example for glutathione described in this article: https://drknews.com/...immune-disease/
 

I didnt know much about that.

 

Melatonin also increases mitochondrial Glutathione and other antioxidants:

https://pubmed.ncbi....h.gov/17349019/

 

 

This study compared the effects of melatonin supplementation on markers of oxidative stress, and on the activity and expression of antioxidant enzymes in the liver of young (3-month-old) and aging (24-month-old) rats. Animals were supplemented with melatonin in the drinking water (20 mg/L) for 4 wk. Liver concentration of thiobarbituric-reactive substances (TBARS), as an index of lipid peroxidation, and the oxidized to reduced glutathione ratio significantly increased in aged rats (+58%), while values did not significantly differ from the young in aged animals receiving melatonin. Significant decreases in the liver activities of Cu,Zn-superoxide dismutase (SOD) (-25%), cytosolic (-21%) and mitochondrial (-40%) glutathione peroxidase (GPx), and catalase (CAT) (-34%) were found in aged rats. Melatonin abolished these changes and also prevented the reduction of Cu,Zn-SOD (-33%), cytosolic GPx (-30%), and mitochondrial GPx (-47%) liver protein content as measured by Western blot. Reductions in Cu,Zn-SOD mRNA (-39%), and GPx mRNA (-86%) levels induced by aging were also abolished by melatonin. In summary, our data indicate that melatonin treatment abrogates oxidative stress in the liver of aged rats, and that prevention of the decreased activity of CAT and the downregulation of Cu,Zn-SOD and GPx gene expression contribute to this effect.

 

 

Vit.C plays a role in mitonchondria, but I wonder if as  we age we shouldn't focus more on supplements that target mitonchondria more specifically since they become more and more damaged and cause more and more ROS, leading to accelerating senescence. For instance Ubiquinol delays senescence:

https://www.ncbi.nlm...les/PMC4025630/

[QuestforLife]

I am currently a little suspicious of either:

1. The study design - because 1000 bp increase seems unusually large.

or

2. The telomere theory of aging. If telomere lengthening was "rejuvenating", then we should have noticed a result like this (or similar) a long time ago, since the supplements in the study have been taken by millions of people world-wide for decades.

Telomere attrition in tissues is pretty slow in humans, ~70bp/year, which is only about 1 cellular division! Obviously most tissues divide hugely more than this per day,let alone per year.

This suggests the ~70bp/year loss is the rate at which stem cells are losing the fight against normal cellular loss in the body.

Therefore if you looked at bone marrow stem cell telomere loss you'd find it was considerable. Look at this paper using a papaya extract. (https://www.research...n_a_Mouse_Model). Even with supplementation that increased telomerase and antioxidant status, bone marrow telomere length loss was huge.

All these studies in humans only look at leukocytes. There have been centenarians with longer leukocyte telomere length than 40 year olds(see the graphical extract on this paper: https://www.scienced...303661?via=ihub).
If you looked at bone marrow you'd see the real picture. But I don't see any companies offering that service!

For reference two cycles of epitalon lengthened my average leukocytes telomeres by ~300bp and my shortest telomeres by ~1000bp. It's unclear how much this affected bone marrow stem cells however,or whether it is purely an effect on leukocytes.

Edited by QuestforLife, 28 July 2020 - 10:05 AM.