As a follow-up on the previous article posted here on Saturday, December 14, 2024, on:
A Poser: Can Excessive Intake of Vitamin C Cause Kidney Damage?
https://scientificlogic.blogspot.com/2024/12/a-poser-can-excessive-intake-of-vitamin.html
Let me now write a little bit more about vitamin C.
A lot of people believe if vitamins, including vitamin C is good for health, then more is even better? For instance, a deficiency of vitamin C causes survey but what if they take excess of it? Wouldn’t that be better? We shall address this question shortly.
Before we go into that, let’s find out how much vitamin C do we need daily?
There was a famous classical Sheffield experiment done in 1944 on 20 volunteers who were given a diet containing less than 1 milligram vitamin C daily. Three received a vitamin C [ascorbic acid] supplement of 70 milligram daily, 7 received 10 milligrams, and 10 had no supplement. No signs of deficiency were observed in those receiving supplements over a period of 14 months. All 10 of the volunteers receiving no supplement developed clinical scurvy. The first changes were enlargement and keratosis of the hair follicles, beginning after 17 weeks of deprivation. Later the follicles became haemorrhagic and formed the characteristic scorbutic spots. Gum changes began to appear after 26 weeks. One subject developed effusion into both knee joints and ecchymoses of the leg. Two developed cardiac complications. A dose of 10 milligram of vitamin C [ascorbic acid] daily removed all the clinical signs and after 7 to 9 weeks of treatment the skin appeared normal.
The experiment showed beyond any doubt that 10 milligrams. of vitamin C [ascorbic acid] daily will not only prevent scurvy but will also cure the disease. This, of course, does not mean that 10 milligram is an optimum requirement or a recommended daily allowance. In order to cover individual variations and include a safety margin, nutritionists recommend a daily intake of 30 milligram. and thus, are in agreement with the recommendation of the League of Nations Health Organization Technical Committee on Nutrition made in 1938 [this Bulletin, 1938, v. 13, 979].
The Sheffield experiment is a classic example illustrating that only small amounts of vitamin C are necessary, not just to meet basic physiological needs, but also cure scurvy. However, this doesn't imply that 10 mg is the optimal dose for overall health.
Diagnostic Methods for Vitamin C Levels:
But how do nutritionists measure the status of vitamin C in the body? Is it too high, or is it too low people ask?
Due to water solubility of vitamin C, nutritionists use the saturation test to assess the status of vitamin C (ascorbic acid) in the body. If the body is already saturated with vitamin C, it will be shown in the urine rapidly. If there is a deficiency, then there is little urinary output and there will be a delay time in any output as they body will try to retain and absorb the ascorbic acid as long as possible. Unlike drugs that are toxic to the body, the body will try to get rid of them as fast as possible with the shortest retention time.
The diagnostic method nutritionists use to assess the status of vitamin C in the body and also for them to diagnose vitamin C deficiency disease, is the Tillmann-Harris-Ray method.
It consists essentially of the daily administration of 300 milligram of ascorbic acid intravenously, until at least half of this amount reappears in the urine. If the body was saturated, the ejection of this quantity takes place within 1–4 days afterwards. If hypovitaminosis dominates, then the ejection is delayed. So far, by examining blood directly only extreme values can be evaluated: above 1 milligram per cent indicates saturation, while below 0.4 milligram per cent indicates hypovitaminosis. Concentrations ranging between cannot be evaluated properly, because 0.5 milligram per cent may already signify saturation, while in contradistinction 0.9 milligram per cent may, in certain circumstances, indicate hypovitaminosis.
The Tillmann-Harris-Ray saturation test is an interesting and somewhat historical method for assessing vitamin C status. While it highlights the body's capacity to retain or excrete vitamin C based on its needs, more modern methods, such as high-performance liquid chromatography (HPLC), are now used by nutritionists and nutrition biochemists to measure plasma concentration of ascorbic acid levels.
There may be a possibility of error in using such a test owing to the variation in absorption and utilization of vitamin C from the gastro-intestinal tract because of varying degrees of acidity (anacidity), inflammation, the introduction of laxatives and other less understood factors. The same error holds for tests which involve studies of the blood level of vitamin C instead of in the urine after the oral administration of this vitamin C.
Since nutritionists are able to measure how much vitamin C is retained in the body, let us now find out what happens if we take excess of it. This brings us on the philosophy of "more is better"
The idea that "if some is good, more is better" is a common misconception in nutrition. Vitamins, like any other nutrient, have an optimal range—neither too little nor too much is beneficial. The emphasis on a diet rich in fruits and vegetables agrees with current nutritional guidelines, as whole foods provide not only vitamins but also fibre, phytonutrients, and other compounds that work synergistically.
In the 1960s and early 1970s a few cases were reported of a conditioning effect of high-dose vitamin C intake with consequent rebound scurvy upon cessation of supplementation in man. Although these reports do not stand up to scrutiny they are often cited as evidence for such an effect. The same is true for the only published report on two infants with scurvy allegedly induced in utero by moderate vitamin C supplementation of the mothers. Experimental studies in guinea pig and man trying to reproduce a rebound effect have failed. Kinetic studies in man indicate that after high-dose vitamin C intake a large proportion of the vitamin is degraded in the intestine to CO2 by microbiological breakdown. Another large proportion is excreted unchanged in urine. The claim of rebound scurvy due to a conditioning effect of high vitamin C doses is still to be definitively shown.
Risks of “the more the better” Vitamin C are:
1. Risk of Oxalate Stones: While the human body metabolizes most vitamin C, excessive amounts can lead to the production of oxalate, a compound that may contribute to kidney stone formation in susceptible individuals. However, this risk is likely individual-dependent and may not apply to everyone.
2. Tolerable Upper Intake Level (UL): The recommended upper limit of 2,000 mg per day exists to prevent gastrointestinal disturbances like diarrhoea. As mentioned, water-soluble vitamins are excreted if consumed in excess, but this doesn't completely negate the risk of long-term high-dose supplementation.
3. Conditioning Effects: The "rebound scurvy" hypothesis has been debated, but the evidence is inconclusive. However, the body's adaptive mechanisms—such as increased urinary excretion of vitamin C when intake is high—are important to consider when advocating for mega-doses.
Nevertheless, vitamin C might be beneficial in specific contexts, such as improving creatinine clearance after kidney transplant surgery. This is an example of targeted therapeutic use rather than generalized supplementation. Vitamin C's antioxidant properties might play a role in reducing oxidative stress, which can benefit renal health in controlled situations.
The recommended daily amount for vitamin C varies from country to country, generally it is 75 milligrams (mg) a day for women and 90 mg a day for men. During pregnancy, 120 mg a day are recommended. The upper limit for all adults is 2,000 mg a day. Although too much dietary vitamin C is unlikely to be harmful, large doses of vitamin C supplements might cause diarrhoea, nausea, vomiting, heartburn. stomach (abdominal) cramps, and possibly headache. But I think a daily diet rich in fruits and vegetable are more than adequate for the requirements of vitamin C for most people without the necessity of given vitamin C supplementation
However, a slightly higher intake of vitamin C may help decrease the levels of creatinine in our body. For example, a 2021 review found that vitamin C helped increase creatinine clearance in people who underwent kidney transplant surgery.
The risk of toxicity from an overdose of vitamin C might be low as with the B-groups of vitamins, namely, thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate or ‘folic acid’ and cyanocobalamin (B12). These groups of vitamins are water-based and can easily be excreted in the urine when they are taken in excess.
What we explain could serve as a foundation for an educational article or presentation. It balances historical and modern perspectives while emphasizing practical dietary advice. We might consider elaborating on specific subtopics, such as the role of vitamin C in collagen synthesis, immune support, and its debated effects on colds and cancer.
Integration with Clinical Findings:
Incorporating recent studies, such as the 2021 review on the intake of vitamin C and creatinine clearance, could further strengthen our argument.
As already explained, toxicity with vitamin C and other water-soluble B-group vitamins may be low, but this is not the case with fat-soluble like vitamins A (retinol), vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), E (alpha-tocopherol), and vitamin K (naphthoquinones). Fat soluble vitamins cannot be excreted in water-based urine. They are stored in the body's fatty tissue and in the liver.
Fat-Soluble Vitamins and Toxicity
Fat-soluble vitamins (A, D, E, and K) highlight the contrast between water-soluble and fat-soluble vitamins. Unlike water-soluble vitamins, excess fat-soluble vitamins can accumulate in tissues and lead to toxicity. Acute and chronic hypervitaminosis A are well-documented, and the historical anecdote about polar bear liver is both fascinating and illustrative.
Excessive vitamin A intake can cause toxicity (hypervitaminosis A). Acute systemic vitamin A toxicity typically arises when an individual consumes over 100,000 RAE ( RAE stands for retinol activity equivalents), within a short period, often from supplements or high-dose medications. The toxicity symptoms include nausea, vomiting, headache, dizziness, irritability, blurred vision, and muscular incoordination. Acute toxicity is rare and is more likely to occur after consuming synthetic forms of vitamin A, such as the retinoid medication isotretinoin. Mucocutaneous effects include cheilitis and dryness of lips and oral, ophthalmic, and nasal mucosa. The suggested mechanism involves decreased sebum production, reduced epidermal thickness, and altered barrier function. Additional cutaneous effects include dry skin, pruritus, peeling of the palms and soles, and fissuring of the fingertips. Higher doses of vitamin A may lead to telogen effluvium. Severe cases may manifest with bone pain and increased intracranial pressure.
Chronic vitamin A toxicity is associated with prolonged ingestion of excessive vitamin A, typically exceeding 8000 RAE per day. This condition can develop after consuming substantial quantities of animal-based foods rich in preformed vitamin A, such as liver, or through the prolonged use of high-dose vitamin A supplements. The toxicity symptoms include dry, cracked skin, hair loss, brittle nails, fatigue, loss of appetite, bone and joint pain, and hepatomegaly. Chronic retinoid toxicity affects various organ systems. Bone-related effects include bone spurs, calcinosis, and bone resorption, leading to hypercalcemia, osteoporosis, and hip fractures. Central nervous system effects include headache, nausea, and vomiting.
The Eskimos have long been wary of eating the polar bear for this reason, but it's something the early Artic explorers found out the hard way. Ingesting the liver can cause vitamin A poisoning known as acute hypervitaminosis A. This results in vomiting, hair loss, bone damage and even death. Polar bear liver toxicity due to hypervitaminosis A was first reported by Europeans in 1597 when the Dutch explorer Gerrit de Veer wrote in his diary that while taking refuge during the winter in Nova Zemlya (an archipelago in the Arctic Sea in northern Russia) that he and his men became seriously ill after eating polar bear liver.
Fat-Soluble Vitamins and Toxicity
Poisoning due to excessive fat-soluble vitamins (A, D, E, and K) highlights the contrast between water-soluble and fat-soluble vitamins. Unlike water-soluble vitamins, excess fat-soluble vitamins can accumulate in tissues and lead to toxicity. Examples of acute and chronic hypervitaminosis A are well-documented, and the historical anecdote about polar bear liver is both fascinating and illustrative.
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