Your badly mutated GULO (gulonolactone [L-] oxidase) gene has been robbing you of health all your life and limits your lifespan. It’s so badly mutated that the human variant is now called the GULOP pseudogene.
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.
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Here’s what you can do about it to improve your health and increase your lifespan.
Bill Sardi has been a guest of this column twice before, and has an overview of this subject scheduled for the October issue of the Journal of Orthomolecular Medicine. Specifically, we will chat with him about the latest research confirming the practical health and substantial longevity benefits of fully compensating for this defective pseudogene. The operative word here is “fully.” How much vitamin C is required to fully compensate for not having a working GULO gene? The paltry 60 milligrams that is the RDA or the several grams that animals make when they have a fully functioning GULO gene? What does the latest study suggest that the longevity increase can be?
Although humans have relatively low levels of vitamin C in their blood compared to other mammals, due to the lack of a functioning GULO gene, those having higher levels tend to live longer and have less heart disease and cancer, among other deadly diseases. As an example, a 16-year study reported in 2018 called the General Population Nutrition Intervention Trial, showed that the higher the blood levels of vitamin C were, the lower the incidence of cancer and heart disease. (1) The study was conducted by researchers from the USA National Cancer Institute and the Chinese National Cancer Institute. The 16-year study included 948 people aged 53 to 84 years at enrollment. Among participants whose blood vitamin C levels were among the top 25%, the risk of dying from any cause was 25% lower than the risk in participants whose vitamin C levels were among the lowest quarter.
Those whose blood vitamin C levels were among the highest 25% had a risk of dying from cancer or stroke that was 28% lower than participants whose vitamin C blood levels were in the lowest quarter. Likewise, the risk of dying from heart disease was 35% lower than subjects whose levels were lowest.
When subjects with low vitamin C levels (defined as 28 micromoles per liter or below) and normal levels (greater than 28 micromoles per liter) were compared, a normal level was associated with a 23% lower risk of premature mortality and a 38% lower risk of dying from heart disease, in comparison with low levels.
The researchers concluded, “In this long-term prospective cohort study, higher plasma vitamin C concentration was associated with lower total mortality, heart disease mortality and cancer mortality. Our results corroborate the importance of adequate vitamin C to human health. (1)
None of the participants had vitamin C blood levels comparable to what would be expected from persons having a fully functioning GULO gene. How much better would the difference be if the comparison was made to humans who had functioning GULO genes?
A practical technique of partially compensating for the inactive gene is available now, but an even more efficient technique of repairing the gene will be available in the just-around-the-corner future. Yes, the GULOP gene can be repaired and restored to a functioning GULO gene. With the development of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology the repair of many genes became possible.
Let’s review the problem that the GULOP causes before we chat with Bill Sardi about the solutions.
Although I have mentioned the mutated GULOP and the findings of the late vitamin C researcher, Irwin Stone, many times over the 34 years of writing this column, I have never really discussed them in detail. That’s because until now, we didn’t know how to repair that mutated gene. Scientists have learned how to repair the gene in laboratory animals, and they are well along in elucidating how to repair it in humans.
Previously, I have mentioned that in chemist Stone’s more than 40 years of research on vitamin C, he had elucidated that mankind is one of the few critters who cannot manufacture ascorbic acid (vitamin C) in their bodies. Even the many thousands of animals that can synthesize vitamin C in their bodies, also eat many grams of food-grown vitamin C. Most plants also have this gene and can produce some vitamin C.
As many, if not most readers know, the intact GULO gene makes the active enzyme protein, L-gulonolactone oxidase (GLO) in most mammals and thousands of other animals. GLO is a compound required in the process that converts blood sugar (glucose) into ascorbic acid (vitamin C). In humans, the pseudogene GULOP is so damaged that it cannot make GLO and thus, mankind must get vitamin C solely from the diet. However, there is some evidence that this damaged gene can produce some vitamin C in the human fetus and in the neonate (newborn less than four weeks old). Genes become mutated when DNA “base pairs” (the four-nucleobase building-blocks of DNA) are altered or missing. Figure 1 graphically illustrates just how bad the gene is mutated in primates including man.
Figure 1. To illustrate the extent of damage to the human GULO pseudogene black boxes and white boxes marked with an “X” can be used. In this illustration, the black boxes represent the identical portions of the genes in both the rat gene and the human pseudogene. The white boxes marked with an “X” represent portions of the genes that are different due to mutations.
Comparing the human GULO pseudogene to its functional counterpart in the rat genome shows that some regions (called exons) are absent. This is represented schematically in Figure 1. This means that the human GULO pseudogene has only five exons out of the 12 found in the functional rat GULO gene. Other features of note associated with the human GULO pseudogene included one single nucleotide insertion, two single nucleotide deletions, and one triple nucleotide deletion. Researchers also identified additional “stop” codons.
Besides his elucidation of facts surrounding the missing vitamin C gene, we owe our thanks to Irwin Stone for getting Dr. Linus Pauling interested in vitamin C. Dr. Pauling introduced me to Stone while he was reviewing my manuscript for Supernutrition: Megavitamin Revolution. (2) Stone also reviewed my manuscript and on Sept. 13, 1971, he wrote to me, “the proper long-term megascorbic use of ascorbic acid will be the coming breakthrough in Geriatrics.” Well, that was almost 50 years ago. Scientists are now confirming the increased lifespan benefits. Bill Sardi will shortly review for us the recent evidence that is quite amazing and convincing.
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Besides his elucidation of facts surrounding the missing vitamin C gene, we owe our thanks to Irwin Stone for getting Dr. Linus Pauling interested in vitamin C. Dr. Pauling introduced me to Stone while he was reviewing my manuscript for Supernutrition: Megavitamin Revolution. (2) Stone also reviewed my manuscript and on Sept. 13, 1971, he wrote to me, “the proper long-term megascorbic use of ascorbic acid will be the coming breakthrough in Geriatrics.” Well, that was almost 50 years ago. Scientists are now confirming the increased lifespan benefits. Bill Sardi will shortly review for us the recent evidence that is quite amazing and convincing.
As Irwin Stone wrote in his 1972 book, human requirements for vitamin C should be based on comparison to the amount naturally produced by most animals as a liver metabolite. (3) Dr. Andrew Saul listed some of these in our January column. “Animals make a lot of vitamin C, he said, “in the neighborhood of 2,000 to 12,000 mg (2 – 12 grams) per day per human body-weight equivalent. Plus, they make considerably more vitamin C when they are becoming ill. A sick goat might make the human equivalent of 50,000 mg/day (50 grams per day).” (4)
In 1979, Irwin Stone published that, “To correct fully this human genetic defect and banish epidemic chronic subclinical scurvy requires daily intakes of ascorbate equivalent to, at least, the amounts synthesized by the other mammals. Humans kept on a long-term regime of full correction of this birth defect show great salutary benefits in health maintenance, disease therapy and slowing of the aging process.” (5)
