Life Extension Magazine®
With each new discovery, the tragic mistakes of the past become brutally apparent.
In the March 2014 issue of Life Extension® Magazine, an article was published titled:
“When Technology Goes in Reverse.”1
The article revealed that cardiopulmonary resuscitation was described in the Hebrew scriptures, gained acceptance amongst some medical groups, but then its use stopped and started repeatedly over thousands of years.
It was not until the late 1950s that “revival of dead persons” using chest compression and other techniques became universally accepted.
Even more egregious errors were made in finding a cure for scurvy.
Scurvy was so prevalent that shipowners assumed a 50% death rate from scurvy for their sailors on any long voyage.2
Yet scurvy “cures” were demonstrated many times, but then discredited because of mistakes, such as using boiled lime juice that was devoid of vitamin C.2,3
Dr. Linus Pauling is often considered one of the greatest scientists of all time, having won two undivided Nobel Prizes. Much of what we take for granted today in the field of biochemistry is attributable to Dr. Pauling’s pioneering research.4
Above-ground nuclear bomb testing was halted by virtue of Dr. Pauling’s tireless efforts in alerting the world about the dangers of radioactive fallout.5,6
Forty years after Dr. Pauling persuaded Russia and the United States to ban it, the federal government admitted that 15,000 Americans died of cancer caused by exposure to nuclear bomb fallout.7 In the early 1960s, our government denied this risk and sought to imprison Pauling for his efforts to ban above-ground nuclear testing.6
Linus Pauling’s final mission was to identify the benefits of vitamin C that extend beyond curing scurvy.
Analogous to the persecution Dr. Pauling endured in his efforts to ban nuclear bomb testing, much of what he advocated about vitamin C was ridiculed. Serious mistakes were then made when testing vitamin C in humans.
This editorial brings out new information about optimal use of vitamin C, some originating from what Linus Pauling espoused decades ago.
When one eats processed foods containing nitrosamine precursors (hot dogs, bacon, ham, sausage), vitamin C can help neutralize this carcinogen in the stomach.8,9
Beyond this benefit, the purpose of ingesting vitamin C-rich foods and supplements is to achieve consistent levels of vitamin C in the blood.
The challenge is that vitamin C is only partially absorbed at doses above 200 mg and then rapidly utilized throughout the body.
A typical vitamin C supplement provides a few hours of elevated blood levels that then return to baseline.
One way of partially overcoming this obstacle is to take vitamin C several times throughout the day, which creates a compliance issue for most people.
Absorption of Differing Vitamin C Doses
Figure 1: The red line on the chart below shows a sharp increase in blood (plasma) vitamin C levels at 200 mg daily dosing. The blue line depicts the smaller additional increases in response to higher vitamin C doses (400-2,500 mg).10
For intakes of vitamin C up to 200 mg, 70%-90% of the ingested vitamin C is absorbed as indicated by the plasma levels achieved.
At doses greater than 200 mg, the proportion of absorbed vitamin C decreases
Therefore, although higher doses (400-2,500 mg) result in greater plasma levels, the proportion of the dose that is absorbed is significantly diminished.
A new formulation overcomes this limitation, resulting in a greater proportion of the vitamin being absorbed and remaining at a higher and sustained blood plasma level throughout the day.
Higher Doses Only Partially Work
What some people do is take higher vitamin C doses (1,000-2,500 mg) that provide a slightly longer degree of acting protection.
These higher doses, however, do not increase vitamin C blood levels at the same rate that occurs with the initial 200 mg dose.
To put this in perspective, the body rapidly absorbs the initial 200 mg of vitamin C swallowed, and partially absorbs some of the excess beyond 200 mg. The remainder is removed through the bowels, sometimes in the form of diarrhea.
Some people use high-dose vitamin C powder combined with magnesium and/or potassium as a laxative.
The primary objective, however, is to achieve higher and sustained vitamin C levels in the bloodstream and cells.
Figure 1 on this page shows vitamin C plasma levels spiking sharply higher with the first 200 mg taken daily, with only modest plasma increases at doses ranging from 400-2,500 mg.
Horrors in Those Who Survived
Historic accounts of scurvy reveal it caused some of the worst medical disasters faced by sailors at sea.
A 16th century surgeon describes his ordeal with scurvy as follows:2
“It rotted all my gums, which gave out a black and putrid blood. My thighs and lower legs were black and gangrenous, and I was forced to use my knife each day to cut into the flesh in order to release this black and foul blood. I also used my knife on my gums, which were livid and growing over my teeth… When I had cut away this dead flesh and caused much black blood to flow, I rinsed my mouth and teeth with my urine, rubbing them very hard… And the unfortunate thing was that I could not eat, desiring more to swallow than to chew… Many of our people died of it every day, and we saw bodies thrown into the sea constantly, three or four at a time.”
If only we could travel back in time to enlighten these sailors that scurvy could be eradicated by ingesting just a few fruits and vegetables.
Our challenge, however, would be the same as it was for others who were ridiculed for showing that citrus protected against scurvy.
Millions needlessly perished from scurvy when the cure was so tantalizingly close.
Most Animals Make Their Own Vitamin C—But Humans Don’t!
The need for vitamin C is so critical that most species have a built-in mechanism to internally convert glucose into vitamin C.11
If you observe gorillas or chimps in the wild or a zoo, you may notice they frequently eat vitamin C-rich fruits/vegetables.
Doing so provides their bodies with a continuous flow of vitamin C.
Humans, guinea pigs and most primates are among the few mammals that cannot produce vitamin C internally11—it must be obtained from food, supplements, and/or infusions.
If vitamin C is not included in guinea pig chow, they die of scurvy, the same way humans do when they are severely vitamin C deficient.
What are Optimal Vitamin C Doses?
Vitamin C was discovered in the 1920s and first synthesized in 1933.12
The ability to precisely dose vitamin C enabled scientists to ascertain minimum levels of ascorbate (vitamin C) toeradicate scurvy in modern societies.
Conclusive proof of vitamin C’s efficacy resulted in Hungarian biochemist Albert Szent-Györgyi being awarded the Nobel Prize in Physiology for Medicine in 1937.13
This breakthrough ended the controversy as to what caused scurvy and the only effective therapy, which is vitamin C.
Hundreds of scurvy treatment attempts were made over many centuries. The cure turned out to be adequate vitamin C, found in most fresh fruits and vegetables.
As knowledge of vitamin C’s other effects arose, lively debates erupted as to how many milligrams of vitamin C are needed to obtain optimal benefits.
The federal government has increased the daily value of vitamin C most Americans should ingest to 75 mg to 90 mg.14 While this dose prevents scurvy, it appears inadequate to fully garner vitamin C’s other lifesaving effects.
Vitamin C Holds Our Body Together
Our skin, bones, teeth, gums, ligaments, blood vessels, and other body structures are held together by collagen.15
Vitamin C is required for continual renewal of collagen throughout our body.15 I emphasize “required” because our structure literally falls apart without adequate vitamin C.
Vitamin C performs many functions, including promoting immunity and creating certain brain neurotransmitters.16,17
But for simplicity’s sake, when one realizes that our body undergoes continuous renewal that is vitamin C dependent, the desirability of maintaining sustained ascorbate blood levels throughout the day becomes strikingly apparent.
One of the leading causes of disability and death in the U.S. is cardiovascular disorders.18
By enhancing collagen synthesis and supporting nitric oxide production, vitamin C offers protection and improves the function of the inner lining of cells in our blood vessels or endothelium.19
If one looks at virtually all health problems inflicted by aging, be it tooth loss, osteoporosis, atherosclerosis, organ dysfunction, and wrinkled skin, vitamin C plays a critical role in a biochemical symphony that sustains our life.20-24
Published data suggest that doses higher than the 90 mg a day of vitamin C recommended by the federal government can yield greater benefits.21,25,26
Markedly Higher Vitamin C Blood Levels
Figure 2: A new “hydrogel” liposomal formula yields elevated vitamin C blood levels with once-a-day dosing. It reduces the need for higher doses that cause some people gastrointestinal upset. This graph shows total vitamin C plasma exposure increased almost seven times in response to this new hydrogel formula compared to regular vitamin C.28
Achieving Sustained and Higher Vitamin C Blood Levels
Figure 3: When looking at the half-life of vitamin C in plasma, taking one capsule daily of a new hydrogel-encased liposomal vitamin C will result in significantly higher vitamin C plasma levels that persist for 24 hours. The chart to the right is a simulated model based on the half-life of vitamin C in blood plasma, precisely measured in a clinical study that compared liposomal hydrogel-encased vitamin C to regular vitamin C.
Modern Day Research Mistakes
Research published in the 1950s showed that taking 500 mg of vitamin C three times a day for only two to six months, reduced arterial plaques, which are associated with coronary artery disease, in 60% of human study subjects with atherosclerosis.27
More recent findings have identified specific mechanisms by which vitamin C improves vascular health.26
Yet studies utilizing single daily-dose vitamin C supplements have not always yielded reductions in heart attack risk.
One obvious reason is that there are over 17 independent risk factors that cause arteries to clog during normal aging. Expecting vitamin C by itself to prevent strokes and heart attacks is irrational.
Another reason why vitamin C has not demonstrated more robust results is that taking a single daily dose provides only limited protection. Within a few hours of ingesting vitamin C, blood levels return to where they were before the supplement was taken.
Up until now, the only way of achieving continuous vitamin C blood levels was to ingest it in food or supplement form throughout the day and night, something that is impractical for most people.
To put this into perspective, most mammals synthesize vitamin C internally 24 hours a day. Humans don’t synthesize any vitamin C.
Perhaps the greatest blunder made in research that seeks to identify vitamin C’s other benefits is dosing it just once or twice daily. This leaves the body with less-than-optimal ascorbate levels throughout most of the day and night.
A Practical Solution
Many of you take supplements several times a day and obtain more consistent vitamin C blood levels compared to people who take a multivitamin just once a day.
Scientists at Life Extension® have spent the past several years searching for ways to formulate a supplement that provides sustained vitamin C blood levels.
We’ve been aware of companies that offer “lipo-somal” vitamin C supplements. We’ve been unable to validate if they provide long-acting protection.
If you look at figures 2 and 3, a new liposomal “hydrogel” formula not only elevated blood-plasma vitamin C exposure 6.8 times more than regular vitamin C, but it also achieved higher levels over an extended period.
Based on daily use of this novel formula, one can obtain sustained, accumulated higher vitamin C blood levels providing all-day/all-night protection.
Look Forward to Future Research Findings
Life Extension® donates supplements to physician-scientists who use them in clinical trials to ascertain efficacy against a wide range of degenerative disorders.
In 2021, a study was published using 20 mg melatonin capsules that Life Extension® specially formulated to study on non-small-cell lung cancer patients.29 We also provided identical-looking placebo capsules for this outside research group.
The box on this page highlights the improved survival in those receiving 20 mg of melatonin compared to placebo.
We look forward to donating this first-of-its kind vitamin C formula to scientists in upcoming trials to see if providing people with 24-hour higher vitamin C blood levels yields greater benefits.
I also look forward to adding this new formulation to my personal program to see if there are improvements in my clinical measures of biological aging.
For longer life,
William Faloon
Daily evening melatonin prolongs survival among patients with advanced non-small-cell lung cancer
- 20 mg melatonin as an adjunctive to standard chemo treatment.
- Reduced risk of death by 39%.
- Individuals with normal baseline sleep had a median survival of 17.6 months with evening melatonin compared to 10.4 months in the placebo group.
Acknowledgments: We would like to thank William Faloon of Life Extension for providing melatonin and placebo for this study.
Biological Rhythm Research. 2021:1-15.
References
- Available at: https://www.lifeextension.com/magazine/2014/3/ when-technology-goes-in-reverses. Accessed August 16, 2021.
- Available at: https://www.sciencehistory.org/distillations/the-age-of-scurvy. Accessed August 16, 2021.
- Lee S, Choi Y, Jeong HS, et al. Effect of different cooking methods on the content of vitamins and true retention in selected vegetables. Food Sci Biotechnol. 2018 Apr;27(2):333-42.
- Available at: https://www.britannica.com/biography/Linus-Pauling. Accessed August 18, 2021.
- Available at: https://www.nobelprize.org/prizes/peace/1962/pauling/biographical/. Accessed August 18, 2021.
- Available at: https://www.britannica.com/biography/Linus-Pauling/Humanitarian-activities. Accessed August 18, 2021.
- Available at: https://www.cnn.com/2002/US/03/01/nuclear.fallout/index.html. Accessed August 19, 2021.
- Robles H. Nitrosamines. In: Wexler P, ed. Encyclopedia of Toxicology. Oxford: Academic Press; 2014:584-5.
- Tannenbaum SR, Wishnok JS, Leaf CD. Inhibition of nitrosamine formation by ascorbic acid. Am J Clin Nutr. 1991 Jan;53(1 Suppl): 247S-50S.
- Levine M, Conry-Cantilena C, Wang Y, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3704-9.
- Chatterjee IB. Evolution and the biosynthesis of ascorbic acid. Science. 1973 Dec 21;182(4118):1271-2.
- Carpenter KJ. The discovery of vitamin C. Ann Nutr Metab. 2012;61(3):259-64.
- Available at: https://www.nobelprize.org/prizes/medicine/1937/szent-gyorgyi/biographical/. Accessed August 19, 2021.
- Available at: https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/. Accessed, August 6.
- Available at: https://www.ncbi.nlm.nih.gov/books/NBK507709/. Accessed August 16, 2021.
- Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017 Nov 3;9(11).
- Harrison FE, May JM. Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radic Biol Med. 2009 Mar 15;46(6):719-30.
- Available at: https://www.cdc.gov/chronicdisease/about/index.htm. Accessed August 16, 2021.
- May JM, Harrison FE. Role of vitamin C in the function of the vascular endothelium. Antioxid Redox Signal. 2013 Dec 10;19(17):2068-83.
- Malmir H, Shab-Bidar S, Djafarian K. Vitamin C intake in relation to bone mineral density and risk of hip fracture and osteoporosis: a systematic review and meta-analysis of observational studies. Br J Nutr. 2018 Apr;119(8):847-58.
- Available at: https://lpi.oregonstate.edu/mic/vitamins/vitamin-C. Accessed August 6, 2021.
- Iwasaki M, Manz MC, Taylor GW, et al. Relations of serum ascorbic acid and alpha-tocopherol to periodontal disease. J Dent Res. 2012 Feb;91(2):167-72.
- Ravetti S, Clemente C, Brignone S, et al. Ascorbic Acid in Skin Health. Cosmetics. 2019;6(4):58.
- Gillis K, Stevens KK, Bell E, et al. Ascorbic acid lowers central blood pressure and asymmetric dimethylarginine in chronic kidney disease. Clin Kidney J. 2018 Aug;11(4):532-9.
- Schlueter AK, Johnston CS. Vitamin C: Overview and Update. Journal of Evidence-Based Complementary & Alternative Medicine. 2011;16(1):49-57.
- Morelli MB, Gambardella J, Castellanos V, et al. Vitamin C and Cardiovascular Disease: An Update. Antioxidants (Basel). 2020 Dec 3;9(12).
- Willis GC, Light AW, Gow WS. Serial arteriography in atherosclerosis. Can Med Assoc J. 1954 Dec;71(6):562-8.
- Akay Internal Study. Liposomal hydrogel vitamin C pharmacokinetics. Data on file. 2021.
- Grutsch J, Hrushesky W, Lis C, et al. Daily evening melatonin prolongs survival among patients with advanced non-small-cell lung cancer. Biological Rhythm Research. 2021:1-15.