Pharmacokinetics
and Pharmacodynamics of Ascorbic Acid (AA):
[What the ½ hour blood half-lifetime means]
Pharmacokinetics (Pk) is what the body does
to the drug; pharmacodynamics
(Pd) is how the drug effects the body and its target organs, biological
functions, chemical processes and/or microbes and parasites.
AA Pk deals with how it is administered effectively
in what form, amounts and frequencies.
AA is in foods, more in certain sources. AA is supplemented by oral uptake in the gut, by injection and
via IV infusions directly into the blood.
Pk deals with rates of change in concentration and how & where it is
distributed, stored, converted, metabolized and eliminated.
If oral AA intake is in the GI tract, too much can make your gut loose. “Too much” is highly variable over a range of more than 200 to one, depending on medical condition. AA in too high levels causes a gut purge, changing the gut environment. Natural gut purging during an illness is not a bad thing if you are prepared to reboot the gut with probiotics.
Take less AA and things go back to normal. The intake level at which the loose bowel condition occurs depends on AA utilization and on the ROS oxide chemical stress levels inside the body. The RDA recommended daily allowance is a single number based on long-term low AA input and non-depleted AA storage in the body, for healthy persons with negligible ROS and stresses.
The high range of pathological, condition-driven AA-needs calls for much more AA than can be stored. A 100 kg stressed rat would make 17-20 grams of AA from glucose in its liver, continuously, over the day as it is consumed neutralizing toxins and stress in the rat. Sometimes sick rats need even more. So it is reasonable for people to take AA continuously at this level, or higher. Normal diet does not even come close to supply this much AA. Hyperglycemic (diabetic) conditions block and reduce AA cellular uptake and absorption, requiring additional 3+ to >6 grams of AA daily to reach normal effectiveness. AA and CoQ10 work together to protect intracellular mitochondrial DNA from damage. See Ely.
After about a half hour after intake, AA is working
and within 1 hour the intake is fully in your blood. AA in the blood is highly variable. It is absorbed by store-house
organs, like the eyes, and vision changes may be quickly evident. The first time I started a high dose of AA,
within a half hour my eyes snapped into focus. The lenses of your eyes are AA
storehouses, you may be able to use the daily changes in focus as an indicator
of AA changes, to remind you that you need to eat some more AA.
Reactive oxide (ROS and NOS) molecules metabolize
AA. When they come in contact with AA molecules, they convert the AA to the
dehydroascorbic (DHA) form, which is a mild oxidant. The spent, metabolized DHA is excreted. Tests for antioxidant AA
in the urine do not react to the DHA.
Cancer cells in tumors have a huge uptake appetite for DHA, converted
from AA. DHA then kills the cells in the tumor, acting on the cancer cells
mitochondria. AA in normal cells, in
the absence of inflammation, is non reactive and it does not endanger cells,
but has a protective action against toxin and allergens. AA’s cellular uptake is much lower than DHA.
When the blood has excess AA and the storage
threshold has not been achieved, it is quickly stored for later use. Accounting
in part for the short half-lifetime as it is absorbed into the storehouses.
When the body has a shortage, or an organ under attack (or a tumor) has a
shortage, the AA moves from the storehouses to the blood and to the place of
need where it is oxidized and metabolized.
The DHA form is sucked into infected/cancer cells and helps them to die.
Excess DHA form passes back to the lymph and blood and is later excreted
through the kidneys.
When we are very healthy and contain few or no
microbial parasites and chronic infections, we might get by with about 100
milligrams per day. Building up quite a stored reserve. When the reserve goes critically low, blood
levels drop and we start to feel uncomfortable. When we are borderline depleted and when we encounter an
allergen, we have an allergic attack.
If we have hay fever, we are chronically low in AA. When we have high AA
reserves, we do not have any hay fever.
When AA levels are low (scurvy), cortisone levels
increase, suppressing the immune system. This makes it easier for invading
microbes and chronic microbes to replicate. We get sicker, producing more
reactive oxides, which further deplete the active AA that is left. Histamine levels rise to have a protective
effect for some cells. When AA levels
pass a too-low threshold level, ROS and histamine levels rise exponentially.
If we were
sick with a hemorrhagic fever like Marburg
we might need 250 grams of AA per day and that amount might not be
enough. When you have cancer you need a
lot more AA to feed the tumors and if it is not supplied frequently you die of
scurvy. AA taken frequently for end stage cancer will ease the misery related
to the scurvy state created by the cancer stealing the AA from the rest of the
body. At still higher IV levels, 100-200 grams/day, AA in the form of sodium
ascorbate kills the cancer cells.
When you are acutely sick, you burn AA rapidly, and
any stored AA is sucked out of the storehouse organs. You feel this as a
feeling of sickness until it is replaced.
If your brain, eyes, and body have a dull ache, this is the sign of
depleted AA. When I get the flu, I take
six+ grams of AA every 2 hours and the discomfort eases or almost vanishes. I
used to have low AA levels and hay fever during pollen season. With high AA levels, I never have seasonal
hay fever.
The Pub-Med
articles that say that AA’s blood-concentration half-lifetime is ½ hour
although correct for the conditions measured, in the dynamic-AA-needs world of
pathologic-condition-nutrition a
precise dosage cannot be determined in
most circumstances. The
pharmacodynamics of AA in vivo is highly dynamic and highly
circumstantial. If the ~100 gram RDA
were to work for healthy persons, with a high balance of stored AA in their
system, the half-life of ½ hour would be related to intake and excretion alone.
Actually a low blood-level of AA is supplemented from stored reserves. More
modern info-sources recommend a healthy person RDA of about 3 grams. Older folks with many microbial parasites
(chronic infections with inflammation) need 6 to 12 grams per day, sometimes
more. Some toxins need high AA intake
to fully neutralize additional ROS produced by the toxin and the toxin itself.
Active AA in the blood is diminished by transit to storage, by
metabolism, by attacking oxides, and by excretion. Klenner himself tested
active AA excretion in the urine with Benedicts reducing
glucose test, while he was applying high AA dosages for very sick persons.
He used frequent urine tests as a dynamic indicator of how much AA to use. He found that during the illness, while he
was putting large amounts of AA into the patient, that no reducing AA showed in
the urine. After resolution of the
illness, reducing AA started showing in the urine, and he knew that the
recovery was almost complete.
It is illuminating to compute how long AA can stay in the blood at
effective levels. Pretend that the ½
hour half-lifetime is correct. A
two-hour delay after AA administration implies a depletion to 1/16 the initial
level. An eight-hour delay in re-intake
means the AA blood level depletes to near zero. In the presence of a systemic acute disease condition, the AA is
much more rapidly oxidized than given in the numbers below. This shows why frequently repeated
(never-a-missed-dose) oral AA supplementation is needed.
Hrs/Depleted-to-Level%= .5h/50%; 1h/25%; 1.5h/13%;
2h/6%; 4h/.4%; 6h/.02%; 8h/.00% = 2.5*2-15%.
This means that once a day AA intake in AA
depleted (scurvy) state the level next day is 1/248. This also means
that if you are attempting to verify Klenner and Cathcart’s work you must use
valid pharmacokinetics and have to have oral intake every 2 hours as they
recommended.
Think of AA as a food and
eat some with every meal.
Most of the historic AA testing experiments
are worthless, because they failed to follow the proper amount, method, or
frequency of AA administration. Most experimenters were testing the depleted AA
state and thus their “AA is useless” findings are falsified by their faulty
methodology. Klenner, Cathcart,
Pauling, Kalokerinos confirmed each other, using appropriate pharmacokinetic
intake levels and frequencies. Others
throughout the world have confirmed these scientists, if they follow their
methods and/or exceed their dosages and frequencies.
If you do meta-studies of a bunch of
now-falsified “AA-failed” studies, you will have produced incorrect
consensus-supporting conclusions. Thus
the mistakes have propagated for a period of about 65 years. Bad science was in a falsified-concept
feedback loop. “Absence of evidence” is
not “Evidence of absence”. We can’t be
all wrong. But most of the consensus was wrong and the consensus was ignoring
published successes. See the reasons.
The AA ignoring continues. Some savvy nutritionists
worry that an effective nutritional AA modality might be suppressed based on
regulator prejudice, ignorance or the drug companies’ lobbying to limit
effective and low cost competition.
Glucose – AA antagonism:
John Ely has a paper discussing neglected “Unprofitable Modalities” of medicine that are underutilized, greatly to our detriment. See: On the Science of Essential Nutrients By John T.A. Ely.
He defines the change in our diet around 1910
when more sugar and refined starches came into vogue. Current “normal” glycemic levels are high compared with the
levels of 1910. Hyper glycemic high
glucose levels block the action of AA, making it necessary for intake to be
higher than 10 grams per day. The way
to successful treatment is to apply Aggressive Glucose Control (AGC) by
reducing carbohydrates to the levels of benign ketosis. This is Dr. Atkins’
induction stage diet. See Ketonic AA
Protocol.
The benefit of AGC is to enhance the effect
of AA as an antibiotic/antiviral and to help DHA uptake into infected and
cancer cells, where the oxidized AA (DHA) acts to kill the cell invading
dysfunctional mitochondria, and to enhance the immune cell functionality to
attack invading microbes. With AGC, the AA below the 10 grams per day intake
level, the AA has its normal protective, anti toxin and immune stimulation
benefits.
Successful clinical Results:
The site, DoctorYourself.com, has material documenting successful high dosage AA IV treatments. See: Intravenous Ascorbate as a Chemotherapeutic and Biologic Response Modifying Agent by The Center for the Improvement of Human Functioning, International, Inc., Bio-Communications Research Institute.
Successful application of AA IV to treating various cancer conditions needs to meet the criteria below.
Criteria: A valid treatment-trial
should include providing tested (not assumed) blood AA levels that are high
enough concentrations to exceed the killing concentrations for cancer cells in
vitro. Papers exist with in vitro
cancer-cell-killing AA concentrations published for various cancer cell
lines. The duration of the AA blood
levels at a killing-concentration must include several hours each day of
maintenance at more than the effective concentration. They should also include
oral AA intake at high levels at 2 hour intervals to avoid AA depletion between
IV sessions.
Pharmacological effects of
AA:
All humans lack an essential gene, so we all must eat AA several times each day in sufficient levels appropriate to our daily needs.
First, AA is an antioxidant and it disables the reactive oxidizing species (ROS) that it encounters. Next it has a huge number of additional biochemical actions. Including healing in heart disease.
Our ongoing AA web research: AA vs. Cancer
In Cellular Health Series: Cancer by Matthias Rath, MD, has an illustrated color insert: The Victory Over Cancer is at Hand. Microbes invade the host’s leukocytes (macrophages) and/or other (liver, tissue, etc. cells), take over intracellular gene-driven enzyme production, and produce an imbalance.
Rath, in the insert, describes how a nutrient cocktail stops the destruction of tissue by viral-infected cancer cells. The coctail ingredients are a combination of L-lysine, L-proline, Vitamin C and Epigallocatechin Gallatin (EGCG, a green tea extract). AA disables the spreading-factor enzyme, hyaluronidase produced by viruses, cancer cells and bacteria. Hyaluronic acid is a long chain sugar molecule that is one thread in the three-dimensional woven-matrix that makes up the structure of our tissues.
If you combine hyaluronidase and a few select protein-eating enzymes you can dissolve the tissue that is generated to wall off tumors. Cancer cells generate all of these enzymes to facilitate metastasis. The Lysine and Proline act as targets for these protein eating enzymes, blocking their action on tissues.
Hyaluronidase (HD) enzyme is made by microbe parasites. It digests the hyaluronic acid lubricant in the joints that protects cartilage. AA plus L-lysine is known to facilitate healing of Herpes-caused lesions. AA disables the HD in your system, slowing or stopping germ spreading and protecting the HA in the joints. It also plays a role in rebuilding tissues and joint cartilage. AA also facilitates wound and surgery-healing, and stem cell differentiation in healing joints.
AA is
a powerful and quick-acting ant-toxin with a wide range (almost universal) of
toxin neutralization applications. See:
Early
Clinical Usage of Vitamin C by Dr Frederick Klenner. It
is surprising that emergency rooms inject adrenaline to stimulate AA release
from our glandular storehouses instead of using large amounts of AA
directly. Many are taught that
adrenaline works but are not taught that much of the results are from AA and
that more AA injected directly will work better and in a safer manner.
Suggested
amounts and rates of Vitamin C intake:
Depends on body weight and conditions.
Use
ratios:
Your Suggested Daily Intake (Grams) = [Your weight (Kg)] x [17 (grams)/200 (kg)]
If
you are almost Well: 6 to 17 grams for a 200 lb = 100kg person.
According to Vojdani and Franco, Six grams of AA per day, at a minimum, will begin to restart the immune system’s T-cells’, B- cells’, and Macrophages’ recovery from the mitochondrial dysfunction (MD) that is a result of various microbes invading these immune system cells. These are white blood cells. 6 grams/day = 4x500 mg tablets (= 2 grams) every six waking hours, 3 times/day. For higher levels you may wish to build up slowly to bowel tolerance. If diarrhea occurs, decrease by 1 gram and work up to higher levels. This is your individual tolerance. Spread the dose over the day for maximum benefit.
A typical daily multi-vitamin contains only 50-100
mg of vitamin C. This is 1/20th to 1/10th gram, just
enough to prevent scurvy if you are healthy, but not nearly enough to
neutralize serious oxidative stress or to prevent infections and other
illnesses. The best form of vitamin C is the one most readily absorbed.
Powdered AA in gelatin capsules is better than
pressed solid pills. Buffered powder
(e.g., Ester C is calcium ascorbate) is available under various house brands,
although sodium ascorbate is preferred.
All of these are available online and frequently quantity discounts are
available.
If
you are Acutely Ill or have Toxin or venom Poisoning:
·
Up
to 100 grams per day. Divide the daily dose and administer 2 to 4 times per day.
·
If
seriously ill or in shock front-load with higher amounts at the start.
·
Use
AA injections and AA by oral intake together.
·
Inject
Intra-Muscular and/or inject Intra-Venous solution (for shock and
unconsciousness)
Chronic: Fibromyalgia, Chronic
Fatigue Syndrome, Lyme Disease, Taking Statins, etc
Depends
on the condition, see Dr. Cathcart’s table below:
Acute
Illness: Oral
dosage to ramp up without limit until bowel tolerance level is determined. Start at dosages depending of severity of
illness, per Dr. Cathcart’s table.
Severe colds may need 30 to 100 grams/day. If your
gut does not go loose, you are below the maximum that you need. If you take AA by injection it does not
affect the gut.
Powder form
in water, 2 tablespoons Vitamin C powder/hour for two days to several weeks,
then decrease gradually. Quitting abruptly might result in “induced-scurvy”
feel-bad condition. So taper down.
Always carry AA on trips, and if headache or
allergic attack or sinus headache, your system is out of AA and you need to
resume prior high AA intake levels.
Vitamin C potentates antibiotics, it reduces allergic reaction to their use, and in high and frequent dosages it stops bacteria spread.
Chronic
Illness:
Polymicrobial infections may need 6, 12, 18, 24, or 32 grams per day of Vitamin
C, with dosages evenly spaced (every 2, 3 or 4 hrs). Timed-release tablets are
worse than spaced dosage. Duration of use of Ascorbate for serious chronic
intracellular infection and cancer may be forever. Transport percentage from
gut to blood depends on the dosage and the degree of need. Higher dosages may
not all be absorbed. Therefore smaller dosages taken more frequently will be
better absorbed than large dosages taken less frequently.
Dose Interval
= 24 Hours/ # of Doses.
Source: Dr. Cathcart’s research at http://www.doctoryourself.com/titration.html
|
ACUTE
CONDITION |
GRAMS
ASCORBIC ACID PER 24 HOURS |
NUMBER OF ORAL
DOSES PER 24 HOURS |
|
Normal |
4 – 15 |
4 – 6 |
|
Environ/food allergy |
0.5 – 50 |
4 – 8 |
|
Anxiety, mild stress |
15 – 25 |
4 – 6 |
|
Mild cold |
30 – 60 |
6 – 10 |
|
Severe cold |
60 – 100+ |
8 – 15 |
|
Influenza |
100 – 150 |
8 – 20 |
|
Coxsackie virus |
100 – 150 |
8 – 20 |
|
Mononucleosis EBV |
150 – 200+ |
12 – 25 |
|
Viral pneumonia |
100 – 200+ |
12 – 25 |
|
Hay fever, asthma |
15 – 50 |
4 – 8 |
|
Burn/injury/surgery |
25 – 150+ |
6 – 20 |
|
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 Yeast |
15 – 200+ |
6 – 25 |
Highest
levels require IV administration. This
is a guide. You should seek Professional Medical Support to administer high
levels of AA by injection or IV. Check
the web for doctors in your community. Look
for orthomolecular and nutrition oriented doctors.
Ketosis Case
History (HK)
Ketosis plus vitamin C (AA) is an adjuvant to the Tetracycline-antibiotic protocol. Combine Klenner's AA and Rheumatoid Arthritis: The infection Connection, Appendix 2 antibiotic protocol. Benign ketosis is induced by drastic reduction of carbohydrate intake. [Atkins-diet induction stage, < 10 grams carbohydrates/day] The liver shifts from fat storage mode to fat extraction mode and fats and proteins are catabolized to acetyl CoA to feed the Krebs cycle where ATP is made to feed energy to all the body cells. Body-cell sugar use shuts down. Hypoglycemic condition stops in ketosis mode. Microbes and viruses are sugar dependent, so are drastically starved. ROS of the sickness oxidizes the AA to the DHA form. Microbes, microbe-infected body and cancer cells need sugar and ingest oxidized Dehydro Ascorbic Acid (DHA) instead. Inside the microbes and the infected cells the DHA oxidizes the cells' mitochondria and induces apoptosis (cell death). AA levels of about 28 grams per day were used in one case history on our website in addition to the Appendix 2 tetracycline protocol to reverse (cure) a severe painful bone-joint resident infection of unknown origin in a period of 4 days. Eating honey-covered peanuts was enough to re-trigger the pain locus. The protocol was repeated successfully several times when relapse was induced by the sugar. The periods of remission extended and severity of relapse decreased with each repetition of the ketosis and the combined protocols.
Other References:
L. Pauling:
Lysine/Ascorbate-Related Amelioration of Angina (Arterial Sclerosis)
[JOM 1991] A remarkable Case History Antibiotics vs. Chlamydia
pneumonia might be added to protocol
http://faculty.washington.edu/ely/paulinglysine.html
Linus Pauling: The
[In-]Effectiveness of the National Cancer Institute
[1977,
After $billions, Still no AA studies]
2004 Petition to
ReEvaluate Vitamin C RDA based on latest scientific findings.
[2012,
Seven years later, Still no corrections to flawed publications and stonewalling
by the NIH researchers still continues:
“Had they exhibited any integrity, NIH researchers should have written medical journals and retracted their previously errant studies. They didn’t. They should have alerted the Food and Nutrition Board that the Recommended Dietary Allowance for vitamin C needs to be re-evaluated. They didn’t. They should have alerted the news media. They didn’t. They should have withdrawn now erroneous printed publications and website pages that continue to air the misinformation. They didn’t. Even after being prodded for over a year by fellow scientists, Drs. Steve Hickey and Hilary Roberts from Manchester, England, the NIH researchers took no corrective action.
“Hickey and Roberts
reacted by writing
a book on vitamin C (Ascorbate: The Science of Vitamin C, available as an
e-book atwww.lulu.com/ascorbate$6.00 US funds) that
documents the scientific mistakes made by NIH researchers….”
The 2004 petition
from noted scientists to NIH remains a milestone marking the start of a new
period of official failure to respond, similar to that noted by Linus Pauling
in 1977. See the website below:
Health Supreme by Sepp Hasslberger [2004]
Vitamin
C RDA is too low: The flawed science and the uncorrected mistakes.
Researchers:
Vitamin C Deficiency Widespread - Link to Heart Disease, Infections, Cancer
“HALF-LIFE FOR VITAMIN C
IGNORED: The
main flaw -- the half life for vitamin C is quite short, about 30 minutes in
blood plasma, a fact which NIH and IM researchers have failed to recognize.
(Half life is the time it takes for half of a substance to be removed from the
body.) NIH researchers established the current RDA based upon tests conducted
12 hours (24 half lives) after consumption. "To be blunt," says
Hickey, "the NIH gave a dose of vitamin C, waited until it had been
excreted, and then measured blood levels."
Because vitamin C is used up
rapidly, a very high single dose of vitamin C would not achieve the same
concentration in the blood serum over time as two divided lower doses. Hickey
and Roberts claim many negative studies using high-dose vitamin C have failed
to recognize this fact and have therefore mistakenly concluded that high-dose
supplemental vitamin C is ineffective.
“RDA NOT FOR EVERYBODY: In the past year Hickey and
Roberts have shaken the confidence of the IM and NIH, revealing that the
medical establishment has failed to investigate the use of high-dose vitamin C
properly, for more than 50 years. Hickey and Roberts have taken the IM and NIH
to task for developing the RDA for vitamin C on studies using only 15 healthy
test subjects. Normal variations would call for a greater pool of test subjects
before establishment of an RDA for hundreds of millions of people.
Furthermore, the RDA is
intended to set a level of nutrient consumption that would prevent disease
(scurvy) among the vast majority (95%+) of the population. Yet smokers (50
million), estrogen or birth control pill users (13 million and 18 million),
diabetics (16 million), pregnant females (4 million) and people taking aspirin
(inestimable millions) or other drugs, have increased need for vitamin C and
comprise more than 35 percent of the population. The current RDA wouldn't meet
the needs of these large subpopulations.
“CONTRADICTORY DATA: Furthermore, Hickey and Roberts confronted the IM and NIH with
their own contradictory data. The IM and NIH claim the saturation point is
reached at a certain concentration of ascorbic acid in blood plasma but later
published a paper showing repeated oral doses could achieve much higher
concentrations, more than three times greater! [Annals Internal Medicine 140:
533-37, 2004]
Because of the short
half-life of ascorbic acid, five 100 milligram doses of oral vitamin C taken at
intervals through the day will raise average blood levels more than a single
1000 milligram dose. Hickey says the blood plasma is not saturated when 1000
milligrams of vitamin C is consumed orally since NIH researchers themselves
demonstrated 2500 mg dose produces even higher concentrations. Hickey and
Roberts claim the minimum supplemental dose of oral vitamin C needed to sustain
blood plasma levels is around 2500 milligrams a day in divided doses in healthy
individuals. Millions of others (smokers, diabetics, etc.) have needs greater
than this.
NIH researchers doggedly
cling to their claim that no more than 200 milligrams of oral vitamin C is
required for human health and that a diet which includes five servings of
fruits and vegetables would provide 210-280 milligrams of vitamin C.
[Biofactors 15: 71-74, 2001] But only 9 percent of the US population consumes 5
servings of plant foods daily. The National Cancer Institute has abandoned
their 5-a-day recommendation and replaced it with 9-a-day servings of fruits
and vegetables once they recognized five servings a day had not reduced the
risk for cancer or heart disease.
“TOLERABLE UPPER LIMIT ALSO
FLAWED: The recommended Tolerable Upper Limit for
vitamin C, 2000 mg per day, gives the false impression that amounts beyond this
would be toxic or produce side effects. In fact, 2000 mg of oral vitamin C
would not meet the needs of millions of American adults. The only side effect
at this dose is transient diarrhea which usually dissipates over time.
“TISSUE LEVELS VS. BLOOD
PLASMA LEVELS: The mistaken idea that high-dose vitamin C supplementation
saturates the blood plasma after a moderate dose of about 150 milligrams of
oral vitamin C, and additional amounts are worthless since they are excreted in
the urine, now must be abandoned, says Hickey and Roberts. More than a decade
ago other researchers found that consumption of high-dose vitamin C (2000 mg
per day) increased ascorbic acid levels in the human eye by 22-32 percent
compared to when a so-called saturation dose (148 mg) is consumed. [Current Eye
Research 8: 751, 1991] Ascorbic acid levels in other tissues in the body, such
as the brain where vitamin C concentration is 10 times greater than in blood
plasma [J Clinical Investigation 100: 2842, 1997], make it evident that blood
plasma levels may not be the gold standard for measuring vitamin C adequacy in
all tissues in the human body.”
Also
see Dr. Klenner’s articles:
The
Use of Vitamin C as an Antibiotic
The
Treatment of Poliomyelitis and Other Virus Diseases with Vitamin C
Dr. Klenner’s 1971 Vitamin C paper
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