Why daily vitamin C supplementation is of key importance?
Scurvy - the sailor’s nightmare
When the first maritime explorers set sail from the ports of their homelands, perhaps they were not expecting a “walk in the park” journey. The sea storms, burning sun, humidity, the weeks and months spent on the ship, without any sight of land seem tough. However, few, if any, knew that their biggest enemy would come from the food, or more specifically the lack of it. Scurvy, the deficiency disease caused by lack of vitamin C in the human diet, was known for at least 3,000 years before its cause was linked to a food factor. Scurvy killed more than two million sailors between the time of Columbus’s transatlantic voyage and the rise of steam engines in the mid-19th century. The problem was so common that shipowners and governments assumed a 50% death rate from scurvy for their sailors on any major voyage. Scurvy affected many of the explorers we learned about in grade school: Vasco da Gama lost his brother to it; Ferdinand Magellan watched it kill many of his men, who had nothing to eat, he wrote, but “old biscuit reduced to powder, and full of grubs, and stinking from the dirt which the rats had made on it when eating the good biscuit.”
The early signs of scurvy in adults include: weakness; pinpoint-size bleeding spots ( petechial hemorrhages) under the skin due to leakage of blood from the capillaries; bruises which develop as bleeding increases; and horny overgrowth of skin around the hair follicles of the arms, legs and abdomen. After about two months, victims develop swollen and bleeding gums, loosened teeth, bleeding into the membranes covering the eyeballs, anemia, extreme dryness of the mouth and eyes, dry itchy skin, loss of hair, extreme weakness, aching legs, and severe joint pains.
Discovery of vitamin C
Credit for first linking scurvy to something lacking in the diet is usually given to James Lind, a British naval doctor who published his famous Treatise on Scurvy in 1753, telling how he cured and prevented scurvy in English sailors by using lime juice. The anti-scurvy factor had been recognized as a vitamin and called vitamin C as early as 1920, but full identification of vitamin Casa pure chemical compound required the combined discoveries of Albert Szent-Gyorgyi in 1928 and Professor Charles Glen King in 1932
What is Vitamin C?
The term vitamin C describes all compounds exhibiting the biological activity of ascorbic acid. Ascorbic acid is a water soluble dibasic acid, with several key functions in the body. Its importance for the organisms is related to the ability to act as an electron-donor(reduce function) in many chemical reactions in the body through its active form ascorbate. Although most species synthesis it, we humans are not amongst them, due to a mutation in the GULO (gulonolactone oxidase) [1] gene, which results in the inability to synthesize the protein. This protein is responsible for several enzymatic reactions, which lead to the synthesis of Ascorbic acid. Therefore, our only source of it is the food we eat and the supplements we take.
Main functions in the body
The metabolic functions of vitamin C fall in two categories, depending on the properties it exhibits. The first main function is as a biochemical antioxidant. From it, the main benefits arise. The second one is as an enzyme cosubstrate.
Antioxidant functions
Ascorbic acid loses electrons (acts like a reducer) easily and, because of its reversible monovalent oxidation to the ascorbyl radical, it can serve as a biochemical redox (short for reduction-oxidation reaction) system. Reducers are substances that have the ability to reduce other substances (cause them to gain electrons). They are opposite to oxidizers(free radicals included), which have the ability to oxidize other substances (cause them to lose electrons). The redox reactions are the quintessence of chemistry as chemistry is the science of electron reactions. Antioxidant function stands for the ability to neutralize (reduce) substances with oxidizing capabilities. This is a key function for the homeostasis of the body, as oxidizing agents tend to be very reactive and oxidize anything they come in touch with, thereby leading to destruction of molecular structures (DNA, proteins, etc.) in the body. Oxidants are one of the main contributers to degenerative diseases.
Cellular antioxidant Functions
As the most effective aqueous antioxidant in plasma, interstitial fluids, and soluble phases of cells, ascorbate appears to be the first line of defense against ROS( reactive oxygen species-oxygen based oxidizers) arising in those compartments. Those species include superoxide and hydrogen peroxide, which can promote the oxidation of critical cellular components.
• Lipid peroxidation. The LDL (low-density lipoprotein) protective action of vitamin E (tocopherol) appears to be dependent on the presence of ascorbate, which by reducing the tocopheroxyl radical, prevents the latter to act prooxidatively.
• Protein oxidation. At least in vitro, ROS species can oxidize proteins to produce carbonyl derivatives and other oxidative changes associated with loss of function.
• DNA oxidation. Ascorbate contributes to the prevention of oxidative damage to DNA, which is elevated in cells at sites of chronic inflammation and in many preneoplastic (precancer) lesions (abnormal change in tissue). In fact, the continuous attack of DNA of unquenched ROS is believed to contribute to cancer, as elevated steady state levels of oxidized DNA bases are estimated to cause mutational events [2].
• NO oxidation. Ascorbic acid protects nitric oxide (NO) from oxidation, supporting the favorable effects of the later on vascular epithelial function, and lowering blood pressure (NO has vasodilation properties).
• Improving iron utilization. Ascorbic acid can reduce ferric ion (Fe3+) to the ferrous form (Fe2+) and form a stable complex with the latter. This allows the vitamin to convert the dominant form of iron in the acidic environment of the stomach to a form that is soluble in the alkaline environment of the small intestine. These effects result in increased enteric absorption of both nonheme and heme iron. In these ways, vitamin C increases the bioavailability of iron in foods. The ferrous form (Fe2+) of iron is also the active form of iron in hemoglobin, as the ferric ion (Fe3+) is unable to bind with oxygen and transport it throughout the body.
• Interactions with other mineral elements. Ascorbic acid can interact with several essential trace elements. It can reduce the toxicities of high levels of selenium, copper, lead, nickel and others- elements whose reduced forms are poorly absorbed or more rapidly excreted.
• Support of pulmonary function. The redox properties of ascorbic acid play an important role in the oxidant protection of the lung [3], which is consistently exposed to high levels of oxygen and toxic gases.
• Support of neurologic function. The brain and the spinal cord are among the richest tissues in ascorbic acid contents. Plasma ascorbic acid concentrations have been positively associated with cognitive performance in older subjects and with memory in patients with dementia.
• Prevention of cataracts. Cataracts are thought to result from the cumulative photo oxidative effects of ultraviolet light from which the lens is protected by three antioxidants: ascorbic acid, tocopherol, and reduced glutathione. The lens typically contain high levels of ascorbic acid, which are lower in aged and cataractous lens. At least 10 cohort studies have found cataract risk to be inversely related to Vitamin C intake [4].
• Diabetes prevention. Diabetic patients typically show lower serum concentartions of ascorbic acid than nondiabetic, healthy controls. Accordingly, reduced serum antioxidant activity has been implicated in pathogenesis of the disease.
Enzyme cosubstrate function
Ascorbate functions as a cosubstrate for at least 10 enzymes that function in electron transport reactions involved in the synthesis of collagen, noradrenaline, peptide hormones, and carnitine; and the metabolism of tyrosine, xenobiotics, steroids, and fatty acids.
• Connective tissue health. Vitamin C is required for wound healing. The vitamin is accumulated at wound sites where it is rapidly utilized. This reflects the function of ascorbic acid in the synthesis of collagen proteins.
• Fatty acids and drug metabolism [5]. Significant number of studies have shown a correlation between vitamin C and cholesterol metabolism, which is believed to be one of the major risk factors for the development of cardiovascular diseases. Vitamin C stimulates the degradation of cholesterol by the activation of hepatic microsomal cytochrome P-450-dependent enzyme, cholesterol-7-a-hydroxylase, the rate limiting enzyme in the catabolism of cholesterol to bile acids (Ginter 1975, Bjorkhem and Kallner 1976). P-450 enzymes are also the main hepatic enzymes responsible for the metabolism of drugs and xenobiotics (xenobiotic is a substance within the organism which is not naturally produced by it)
Immunity and Inflammation
Studies with animal and cell culture have shown vitamin C to affect immune function in several ways:
• Modulation of T cell expression of genes involved in signaling, carbohydrate metabolism, apoptosis, transcription, and immune function [6].
• Support of natural killer cell activity and production of interferons, the proteins that protect cells against viral attack.
• Support of the synthesis of humoral thymus factor and antibodies of the IgG and IgM classes.
Main benefits of high dose of vitamin C
Vitamin C intakes greater than 100-200mg/day result in elevated concentrations of the vitamin in the extracellular fluids. Under such conditions, pharmacological (drug acting) actions of the vitamin occur.
Antioxidant effects
High doses of vitamin C can reduce markers of oxidative stress, which has been implicated as a central mechanism in the development of obesity related diseases (i.e. cardiovascular disease and type 2 diabetes), and a cause of chronic obstructive pulmonary disease and Alzheimer disease.
Antihistamine effects.
High doses of vitamin C can reduce circulating histamine concentrations. On this basis, vitamin C has been used to protect against histamine-induced anaphylactic shock. Ascorbic acid inhibits histamine release and enhances its degradation.
• Common cold. The most widely publicized uses of “megadoses” of vitamin C are in prophylaxis and treatment of the common cold. The main benefits of high dose vitamin C occur in large doses (≥1 g), which have been advocated for prophylaxis and treatment of the common cold, a use that was first proposed some 25 years ago by Irwin Stone and the Nobel laureate Dr Linus Pauling.
Other infections.
• Helicobacter pylori. Randomized trials have shown that vitamin C can reduce seropositivity for H. pylori and protect against the progression of gastric atrophy in seropositive patients [7],[8]. This may be associated with reduced gastric cancer risk for which H. pylori is a risk factor.
• Herpes. Topical application of ascorbic acid reduced the duration of lesions as well as viral shedding in patients with Herpes simplex infection [9].
Cardiovascular health.
The antioxidant characteristics of ascorbic acid allow it to have an antiatherogenic function in reducing the oxidation of LDLs, a key early event leading to atherosclerosis [10].
Anticarcinogenesis
Ascorbic acid has been observed to reduce the binding of polycyclic aromatic carcinogens to DNA and to reduce/delay tumor formations in several animal models. This effect is thought to involve quenching of radical intermediates of carcinogen metabolism. Vitamin C is also a potent inhibitor of nitrosamine-induced carcinogenesis, functioning as a nitrite scavenger. This action results from ascorbate reduction of nitrate to NO, blocking the formation of nitrosamines.
Oxidative stress.
• Ischemia-reperfusion injury. Tissues sustain injury upon reperfusion after a period of ischemia. ROS are thought to contribute to milder forms of tissue injury at the time of reperfusion (e.g., myocardial stunning, reperfusion arrhythmias). Vitamin C has been shown to be protective against ischemia-reperfusion injury in animal models [11].
• Exercise. Vigorous physical activity increases ventilation rates and produces oxidative stress, which is thought to affect endothelial function. Studies have shown that antioxidant supplementation can alleviate muscle damage and protein oxidation induced by exercise. Vitamin C treatment prevented acute endothelial dysfunction induced by exercise in patients with intermittent claudication [12]) calf pain during walking).
Daily dosage.
|
Age |
Male |
Female |
Pregnancy |
Lactation |
|
0–6 months |
40 mg* |
40 mg* |
|
|
|
7–12 months |
50 mg* |
50 mg* |
|
|
|
1–3 years |
15 mg |
15 mg |
|
|
|
4–8 years |
25 mg |
25 mg |
|
|
|
9–13 years |
45 mg |
45 mg |
|
|
|
14–18 years |
75 mg |
65 mg |
80 mg |
115 mg |
|
19+ years |
90 mg |
75 mg |
85 mg |
120 mg |
|
Smokers |
Individuals who smoke require 35 mg/day |
|||
The recommended daily intake for vitamin C is 75 mg for women and 90 mg for men.
Doses of 500 mg up to 1000 mg or more fall into the pharmacological category. In these doses the main benefits of high dose vitamin C are achieved. Vitamin C can be acquired through food or supplementation. The problem with food intake of vitamin C is that its contents in most foods decrease dramatically during storage owing to the aggregate effects of several processes by which the vitamin can be destroyed.
Vitamin C supplementation forms.
Tablets and liquids. The oral administration of Vitamin C is one of the most popular ways for vitamin C administration. However, pharmacokinetic studies indicate that ingestion of single doses of vitamin C greater than 200 mg have lower relative bioavailability [13].
Injection. The IV(intravenous) application is a good alternative to tablets as nearly fool bioavailability of the vitamin C is achieved. However it is not a convenient way for daily supplementation.
Liposomal Vitamin C. Liposomal vitamin C is a very good alternative to injections and IV (intravenous drip). It may actually be easier, because the liposomal vitamin C is not only fully absorbed, but since it is taken orally, it can be used daily and even several times a day. Daily administration of IV and injections are quite unpractical, and are not free of risks.
Certain individuals react to vitamin C with intestinal problems, including diarrhea. Even individuals with a high tolerance to vitamin C will at very high doses eventually experience the same problems. High vitamin C doses are usually prescribed by doctors and other health care practitioners, and are administered in a clinical setting. That’s mainly because of the fact that these doses are injected. The full absorption in liposomal form is a practical way to avoid sticking needles.
Liposome means in old Greek “lipid cell”. Pronounce “lip-o-soom”.
Vitamin C liposomes are absorbed in a very unique manner. Liposomes are microscopic fat balls, the width of a single hair strand. These microscopic fat particles are made from phospholipids and have a cargo load, in the form of a nutrient hidden inside. These phospholipids are the same as in egg yolk or krill oil. The liposomes are absorbed by melting into the human cell, since they have an outer layer (membrane) that is made from the same phospholipids as the cell membrane. The liposome and the cell basically merge like two soap bells will merge when they touch each other. The content of the two spheres will also blend together and in this ingenious way the vitamin C in the liposome is directly delivered into the cell.
Liposomal absorption is very different from intestinal absorption. Most nutrients and drugs are molecules that are too large to be absorbed. The most common way for food absorption is to break down the nutritional molecules to a size where they can slip between the stomach and intestinal cell walls and enter the blood stream. The liver and other organs then re-assemble the molecules. Liposomal vitamin C absorption is very different because it directly enters the cell. The fat layer of the liposome protects the vitamin C from coming into direct contact with the stomach and intestines. This protection prevents the intestinal side effects of ascorbic acid (vitamin C).
Liposomes are designed to minimize intestinal discomfort, since certain individuals have difficulty tolerating vitamin C therapy at the clinically relevant higher doses. The recommended daily dosage for liposomal vitamin C is typically 1,000 mg. In certain cases doctors may prescribe more.
References:
[1] : Li, Y., Shi, C.-X., Mossman, K.L., Rosenfeld, J., Boo, Y.C. & Schellhorn, H.E. (2008) Restoration of vitamin C synthesis in transgenic Gulo-/- mice by helper-dependent adenovirus-based expression of gulonolactone oxidase. Human gene therapy. [Online] 19 (12), 1349–1358. Available from: doi:10.1089/hgt.2008.106 [Accessed: 31 December 2011];
[2] : Halliwell,B.,2000.Am.J.Clin.Nutr.72, 1082-1087;
[3] : See review by Brown, L.A.S., Jones,D.P., 1997, In:Packer, L., Fuchs, J., (Eds.), Vitamin C in Health and Disease, Marcel Dekker, New York, pp. 265-278;
[4] : Vishwanathan, R., Johnson, E.J., 2012. In: Erdman, J.W., Macdonald, I.A., Zeisel, S.H. (Eds.), Present Knowledge in Nutrition, tenth ed. Wiley-Blackwell, Ames, IA, pp. 942-946;
[5] : A. NAGYOVÂ, E. GINTER, Physiol. Res. 43:307 - 312, 1994;
[6] : Grant, M.M., Mistry, N., Lunec, J., et al., 2007, Br.J.Nutr. 97, 19-26;
[7] : Simon, J.A., Hudes, E.S., Perez-Perez, G., et al., 2003, J. Am. Coll. Nutr. 22, 283-289;
[8] : Sasazuki, S., Sasaki, S., Tsubono, Y., et al., 2003, Cancer Sci. 94, 378-382;
[9] : Hamuy, R., Berman, B., 1998. Eur. J. Dermatol. 8, 310-319;
[10] : Atherosclerosis is the focal accumulation of acellular, lipid plaques in the intima of the arteries. The subsequent infiltration by fatty substances (arteriosclerosis) and calcific plaques and the consequent reduction in the vessel’s luminal cross-sectional area reduce blood-flow to the organs served by the affected vessel, causing such symptoms as angina, cerebrovascular insufficiency, and intermittent claudication;
[11] : Bailey, D.M., Raman,S., McEneny, J., et al., 2006, Free Rad. Biol. Med., 40, 591-600;
[12] : Silvestro, A.,Scopacasa, F., Olivia,G., et al., 2002, Atherosclerosis 165, 277-283;
[13] : Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR .Proc Natl Acad Sci U S A. 1996 Apr 16; 93(8):3704-9;
