Let’s resume where we left off. Last month, we discussed the exciting new study that suggests that optimizing the blood level of vitamin C to about 60 µmol can improve health and substantially extend human lifespan. Let’s continue by discussing the mechanism involved.

Passwater: Well, this certainly is an exciting study. Have you experienced anything like this before?

Sardi: I recall that with the publication of Linus Pauling’s book, Vitamin C And The Common Cold, sales of vitamin C pills reportedly soared by 300% and mortality from heart disease declined by 30% at the time.

I get asked, “(W)hy don’t we see vitamin C-supplementing adults living 144 to 216 years?” My answer is, “(W)e may have to wait 50 to 70+ years for this to be observed. Vitamin C pill users generally don’t take vitamin C throughout the day to maintain optimal blood levels.

Passwater: And, they usually don’t start taking more optimal amounts of vitamin C until middle age—not from birth. So, what is the big take-away lesson here from this discovery that started in a laboratory in Canada?

Sardi: The big takeaway news is that human life is being cut short by two-thirds and for the first time we may, by virtue of habitual vitamin C consumption, achieve unusually long healthspan and lifespan. The other option is to repair the broken gene. That is also now an option.

Passwater: How do you think the public is going to react to this preliminary research?

Sardi: I’ve privately shared this information to others and to a man they all impulsively respond, “Oh, I never want to live that long!”

I respond by saying the animals in the study who had their vitamin C replenished throughout the day lived most of their lives symptom free in robust health, without wrinkles, cataracts, grey hair, heart attacks, cancer or mental decline. When healthspan parallels lifespan then people get real interested, particularly about the cosmetic aspects of avoiding wrinkles and grey hair. Who wants to live long and look old if there is an option? The answer to the question: “How long do you want to live?” is: “As long as I am healthy.”

Passwater: Yes, the goal is to live better longer, not just live longer. A second part of your research paper deals with repairing the dysfunctional GULOP gene. Will we be able to restore mankind’s ability to make ascorbic acid as we need it?

Sardi: This must be a hidden secret in genetic research labs around the world. What we have learned is that small molecules found in nature can get into genetic machinery in the cell nucleus and edit genes. This has already been reported for an inherited hemoglobin deficiency disorder called beta thalassemia. The red wine molecule resveratrol has edited a gene and 52% of subjects were cured and others improved. (15)

Passwater: What is the mechanism?

Sardi: The proposed mechanism is this: Many gene mutations are what are called point mutations. At a point along the nucleotide ladder a mutation may occur. There are genetic mutations of omission (missing a nucleotide) on the DNA ladder, or a sequential mutation where the nucleotide is in the wrong order. These are structural mutations on the DNA ladder (DNA is fashioned as a coiled ladder with steps comprised of nucleotides—adenine, guanine, cytosine and thymine). But I am talking about the dynamic aspects of a gene, its epigenetics or protein-making capability. Genes make proteins (gene expression) or cease making proteins (gene silencing) in response to environmental factors like temperature, radiation exposure, food or lack of food.

Apparently, the gene mutation for the GULOP gene is a point mutation. At a certain point along a strand of DNA there is a Start Codon (start signal) and then a Stop Codon (stop sign) to start and stop making proteins.

A sequence of three nucleotides (such as ATG) is used to signal a gene to start making proteins and another sequence of three nucleotides (like TAA) signals to stop making proteins. These are called start and stop codons. Please see Figure 1. What has presumably happened is that there is a premature stop codon (AGC) in the gene that codes for a protein (enzyme) that is required to convert blood sugar to ascorbate. The GULOP gene begins to make the enzyme (gulonolactone oxidase) to convert blood sugar to a sugar-like molecule called vitamin C. If that protein is incomplete, it will be disposed of. No enzyme, no vitamin C synthesis.

There is a biological phenomenon called stop codon read-through. A small molecule can run through the stop sign and permit a complete protein to be formed that is required for enzymatic synthesis of vitamin C. No CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene insertion technology is required to repair the gene. For example, some people with beta thalassemia right now are taking resveratrol pills and editing their own genes. I’m not sure the research community wants the public to know about this. This is going to blow the business of gene editing out of the water because research labs and private enterprises want to control gene therapy and reap large profits along the way. We’re talking about doing this at home without side effects. CRISPR has run into some problems repairing undesirable genes. Let’s just hope free markets are allowed to continue.

Figure 1. Stop and Start Codon in GULOP gene. Courtesy of Bill Sardi

Passwater: Has this been accomplished in humans?

Sardi: Yes, some researchers were subjecting humans to a complete battery of blood tests to see how a nutraceutical molecule derived from olives fared among healthy humans. Every measure of health from kidney and liver function to white and red blood cells counts were normal. But surprisingly, vitamin C levels doubled (from ~24 micromole to ~48 micromole) without vitamin supplementation. (16) A plausible explanation for this: gene editing via stop codon readthrough. This is very exciting stuff.

Passwater: The mechanism needs to be confirmed. We need to see some actual human GULOP genes that have been restored to active GULO genes or at least a higher level of vitamin C.

Sardi: We have the example of resveratrol with thalassemia and so we now recognize small molecules just may perform stop codon read-through. We already know other molecules (aminoglycoside antibiotics) perform stop codon read-through.

Passwater: What is the nutraceutical molecule you are referring to?

Sardi: It is derived from olives and is very difficult and expensive to extract. The point is, this has already been demonstrated in humans, not just lab dishes or animals. The challenge is how to introduce this option to health seekers. Of course, the other option is to take vitamin C pills throughout the day.

Humanity is entering a brave new world. We now have an option to take vitamin C pills four times a day at equal intervals to maintain blood levels that have been shown to extend healthspan and lifespan in laboratory animals, or even better, we can take a pill that appears to switch the GULOP gene back on. Vitamin C pills are widely available, and the public is not wary of taking them. And no prescription is needed.

Passwater: Just how would this compare to some other anti-aging technologies under development?
Clarifying glo, GULO and GULOP

GLO is a protein enzyme called L-gulonolactone oxidase. L-gulonolactone oxidase catalyzes the ninth, critical step of ascorbic acid synthesis from glucose (blood sugar). The precursor L-gulono-1,4-lactone is a readily available product of glucose metabolism through the pentose phosphate cycle.

GULO is a gene that is called “L-gulonolactone oxidase gene.” A gene is not a protein. A gene is a sequence of DNA or RNA that codes for a molecule that has a function. In this case, GULO­­­­ is the gene that encodes for the enzyme GLO.

GULOP is the human remnant of the gene that encodes L-gulonolactone oxidase in most other mammals. GULOP cannot generate a functional enzyme product and is therefore called a pseudogene.
Sardi: The public needs to understand, if what has been posited in the animal lab can be transferred to humans, a tripling of the human lifespan is plausible. This exceeds the lifespan/healthspan doubling of calorie restricted diets or any of its molecular mimics such as the red wine molecule resveratrol. There is far more evidence that vitamin C can achieve superlongevity because there is human mortality data to back it up.

It will cost individuals more not to take vitamin C pills than it will to purchase them. Out of pocket healthcare costs should decline among those who choose to habitually take vitamin C.

I anticipate ridicule for those who espouse the idea of habitual vitamin C supplementation to achieve what none of the prestigious university-based anti-aging labs have accomplished or is in their R&D pipeline. Adoption of vitamin C supplementation by the public could reduce healthcare spending by over $1 trillion. Vitamin C science must have integrity if it is to be widely adopted. It still may be discredited despite the convincing science.

Passwater: What do you foresee as far as adoption of vitamin C technology?

Sardi: There will predictably be naysayers. Physicians will demand a research study. Of course, what is lacking is the gold standard study physicians demand: a double-blind (neither doctor or patient knows which subjects got an inactive placebo pill) placebo-controlled longitudinal (long-term) study. But such a study is impractical, as it would have to last for decades, even if starting with subjects who are age 40 or 50, and cost billions of dollars. Short of such a conclusive study, we must rely upon markers of health or longevity. Another roadblock is scientific censorship. No dietary supplement company can make any claim that their products have anti-aging or pro-longevity benefits as the Attorney General of the United States now declares any such claims to be criminal in nature and deputizes bankers to arbitrarily cancel the merchant account of any company that makes such claims without appeal. So officially, dietary supplement companies are muzzled when it comes to making any claims like this on their websites.

Vitamin C is trapped in a scientific, political and regulatory box canyon. There is no plausible way to produce a conclusive study to brush away skeptics and even so, it is now a criminal offense to say any dietary supplement produces longevity.

There will be certain opposition to this information. That is why I am attempting to spread this message about vitamin C as far and wide as possible, to make it difficult to dismiss or ignore.

There will be a few innovators who will readily adopt this technology without delay. Early adaptors will wait to see what the innovators say, and once convinced, adopt the technology. Late adaptors and laggards will wait till their doctor blesses the idea and for health insurance to pay. They may be six feet under the ground if they wait that long. In 1979 biochemist Irwin Stone wrote this in his landmark report entitled “Homo Sapiens Ascorbicus, a biochemically correct robust human mutant”(6):

Full correction of this gene mutation may be approached by two pathways: The genetic approach, in which the gene is repaired or replaced so it will be capable of directing the synthesis of the active enzyme GLO. This would be a convenient solution to the problem, but the present “state of the art” in genetic engineering is not capable of doing this. Perhaps another 50 years will see this accomplished. Humans would then be able to perform the endogenous synthesis of ascorbate, like the other mammals. If enough is synthesized in response to stress it will reduce the threat of the CSS Syndrome (chronic subclinical scurvy), but may not insure complete freedom from it. Many mammals with the intact gene for GLO and capable of liver synthesis of ascorbate, still suffer from the CSS Syndrome during their lives. They favorably respond to additional exogenous ascorbate.

The pragmatic approach, which has been available for over four decades and successfully practiced by many individuals. This is simply to daily ingest spaced doses of ascorbate in the range normally synthesized by the mammals, and increase the intake in response to stress. A problem here is our imprecise knowledge of the amounts of ascorbate synthesized by the mammals or the amounts required by Homo under particular stresses. This is not too serious a problem as more clinical tests could rapidly fill in our gaps of knowledge. Also, the virtual lack of any toxicity of ascorbate would make “overdosage” a relatively safe procedure.

Fortunately, the overdose point is when bowel tolerance (loose stools) is reached. The late Robert Cathcart, M.D., treated many maladies with pro-oxidant mega-dose vitamin C up to 50 grams a day, but that is not necessary. Pro-oxidant doses generate transient hydrogen peroxide that selectively kill off bacteria and tumor cells without harming healthy cells. This is the therapeutic use of vitamin C.

For those freshly in the grave, they just missed hearing this is probably the last generation to live a shortened lifespan. It was futurist Ray Kurzweil who predicted developments like this given that the speed of new information is increasing exponentially. Remember, all roads lead to vitamin C: • Cancer • Heart disease • Cholesterol • Immunity • Wound healing • Diabetes • Metabolism • Weight control • Stress • Aging • Longevity

Passwater: Thanks for reviewing your August Journal of Orthomolecular Medicine article with us. Where can readers get more information?

Sardi: They may like to read my other articles on my website at www.knowledgeofhealth.com.

I want to end this interview by reminding readers that it was Dr. Richard Passwater’s popular books, Supernutrition: Megavitamin Revolution (1975) and The New Supernutrition (1991), that served to provide the scientific underpinnings for the natural medicine movement and the dietary supplement industry. The younger generation may not recognize his name today, but Richard Passwater saved the dietary supplement industry from scientific embarrassment at the time. We owe a debt of gratitude to Richard Passwater. I wanted him to be among the first to know of this new development. On behalf of many, thank you immensely Dr. Passwater for your tireless work in antioxidant science.

Passwater: Those are very kind words, Bill. Thank you making me aware of your JOM manuscript so that I could call it to our readers’ attention so soon after publication. Your article should encourage people to optimize their blood levels of vitamin c and thus help them live better longer. WF
References: 15. Chowdhury, A.R., Chakravarty, S. and Chakravarty, A. The genetic basis of the clinical diversity of the Trans-Resveratrol therapy in beta-thalassemic and sickle cell anaemia patients. International Journal Pharma Sciences & Research, 8(11) 211-214 (2017). http://www.ijpsr.info/docs/IJPSR17-08-11-002.pdf 16. Lopez-Huertasa,E. and Fonollab, J. Hydroxytyrosol supplementation increases vitamin C levels in vivo. A human volunteer trial. Redox Bi ology 11:384-89(2017). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219601/