We are thrilled to launch our premium Ester-C Vitamin C product at a time of year when many of us, and our clients, will be reaching for a vitamin C supplement to help prevent and treat winter colds and flu.
Ester-C is a highly absorbable, non-acidic form of vitamin C which is scientifically proven to have unprecedented uptake and retention in immune cells, in a convenient 1-a-day dose. It is the vitamin C of choice for anyone serious about achieving high, sustained cellular vitamin C levels cost-effectively and without gastrointestinal side effects.
Many of our clients will be at risk of vitamin C insufficiency resulting from sub-optimal diets or increased need for vitamin C due to oxidative stress or increased tissue utilisation. Choosing Ester-C Vitamin C over a standard product that will be rapidly excreted from the body will make all the difference in reaping the benefits of increased cellular vitamin C levels.
Vitamin C: background
Vitamin C is a water-soluble micronutrient required for normal cell function, growth and development. Humans lack the enzyme L-gulonolactone oxidase and are unable to produce vitamin C from glucose, so must therefore obtain it from the diet.
Dietary sources of vitamin C
Many of us have much lower vitamin C intake than we think. Fruit and vegetables, including citrus fruit, kiwi, mango, broccoli, tomatoes and peppers are all rich sources; however, vitamin C degrades during cooking, processing and storage. 5–9 servings of fresh or frozen fruit and vegetables per day provide ~200 mg vitamin C, but we know that most children and adults in the UK are not even meeting the 5-a-day target.
Vitamin C functions and health benefits
Vitamin C is an essential antioxidant and regenerates other antioxidants. By limiting the damaging effect of free radicals, vitamin C might help prevent or delay the development of certain cancers, cardiovascular disease and other diseases in which oxidative stress plays a causal role.
Vitamin C promotes resistance to infections by boosting the immunological activity of leukocytes. It is involved in carnitine production, energy-yielding metabolism and reduces fatigue. Vitamin C is also needed for collagen synthesis, important for normal function of bones, cartilage, blood vessels, skin, gums and teeth. It aids normal psychological and nervous system function by involvement in neurotransmitter, tyrosine and neuroendocrine peptide production.
Vitamin C deficiency
Vitamin C deficiency is caused mainly by poor diet. Additional risk factors include smoking, pregnancy, low socioeconomic status, genetic predisposition (SNPs in the SVCT transporters involved in enterocyte uptake of ascorbic acid), old or young age, strenuous exercise and clinical conditions associated with metabolic syndrome such as hypertension, diabetes and obesity.
Symptoms of vitamin C deficiency include fatigue, myalgia and weakness that can be explained by impaired carnitine and noradrenaline synthesis. Vitamin C’s role in collagen synthesis explains symptoms of poor wound healing, follicular hyperkeratosis (excessive development of keratin in hair follicles), perifollicular haemorrhages (where hairs within a follicle become twisted and in some cases cause the follicle to bleed), discolouration of the skin resulting from bleeding/bruising and abnormally dry skin. Other symptoms include gum disease, joint pain and bleeding into soft tissues and joints.
While vitamin C deficiency is rare nowadays, cases of scurvy are on the rise in the UK, which is mainly attributed to low socioeconomic status and poor diet. Oxidative stress and inflammation increase the need for vitamin C because it is consumed during inflammation as it reduces free radical activity. Concentrations in the blood and leukocytes rapidly decline during infections and stress. (Frei et al., 1989)
Ester-C Vitamin C – Unique benefits
Ester-C, also known as calcium ascorbate-threonate, was developed in the early 1980s. It is backed by more research than all other forms of buffered vitamin C. In a chemical-free, water-based process, vitamin C is combined with calcium carbonate, resulting in a pH-neutral blend of calcium ascorbate and vitamin C metabolites, mainly calcium threonate.
Calcium ascorbate delivers all the benefits of standard vitamin C; the vitamin C metabolites (other products formed during the reaction) are what make Ester-C uniquely beneficial, as they boost the uptake of vitamin C into cells, specifically the white blood cells (leukocytes). Ester-C has been clinically proven to maintain high levels of vitamin C in leukocytes for 24 hours, making 1-a-day dosing feasible and effective. The prolonged elevation of vitamin C in leukocytes provides optimal immune system support.
With calcium threonate present, vitamin C has been shown to be absorbed more quickly into cells, reach higher levels and be excreted more slowly.
Large doses of standard vitamin C may cause indigestion, particularly when taken on an empty stomach. Other symptoms include nausea, abdominal cramps and diarrhoea, attributed to the osmotic effect of unabsorbed vitamin C in the intestine. Ester-C has a neutral pH, making it significantly gentler on the stomach at high doses compared to standard vitamin C. (Gruenwald, 2006)
Ester-C is free from dairy, gluten, lactose, soya, wheat, yeast, artificial colours, flavours, preservatives and sweeteners; non-GMO; suitable for vegetarians and vegans; halal and kosher.
Ester-C – Research Studies
When compared to standard ascorbic acid, the addition of L-threonic acid (a vitamin C metabolite) increases ascorbic acid uptake.
L-threonic acid is an active metabolite of vitamin C (specifically of dehydroascorbate). Studies show that when added to ascorbic acid, L-threonic acid stimulates ascorbic acid uptake in a dose-dependent manner and prolongs the retention of ascorbic acid in human T-lymphoma cells (Fay et al., 1991; Fay et al., 1994). Ester-C given to rats as a single oral dose of 100 mg/kg resulted in significantly higher plasma concentrations than that from standard ascorbic acid (Lee et al., 2018). The area under the curve (AUC) values of calcium ascorbate were 1.5-fold higher than those of ascorbic acid, and the Cmax value of calcium ascorbate (91.0 ng/ml) was higher than that of ascorbic acid (74.8 ng/ml).
When compared to standard ascorbic acid, calcium ascorbate with metabolites was shown to significantly increase vitamin C accumulation in leukocytes (white blood cells) which are key players in regulating immunity.
Similar findings have been shown in humans: a double-blind, placebo-controlled, four-way crossover study compared three different 1000mg vitamin C supplements (standard and two formulations of calcium ascorbate [1% and 3% calcium threonate with vitamin C metabolites]) with placebo. While no significant difference in plasma vitamin C levels was observed when comparing the different supplements at 24 hours, both calcium ascorbate with metabolites formulations resulted in significantly higher concentrations of vitamin C in leukocytes (P<0.0001) (Moyad et al., 2008).
Bioavailability is similar for Ester-C and ascorbic acid in terms of blood levels, but bioavailability within leukocytes (white blood cells) for Ester-C is 10x greater.
Similar findings were reported from a double-blind, placebo-controlled, crossover trial in which 36 subjects were randomised to receive placebo, 1000mg ascorbic acid or 1000mg Ester-C. Plasma and leukocyte vitamin C levels were measured at baseline and at 2, 4, 8 and 24 hours post-dosing. There were no significant differences between Ester-C and ascorbic acid plasma concentrations and % changes from baseline; however, the % change in leukocyte vitamin C concentration was higher for Ester-C at 8 and 24 hours compared to ascorbic acid (Figure 1).
Vitamin C homeostasis (plasma saturation) is a tightly regulated process and the movement of vitamin C out of the plasma into leukocytes observed with Ester-C may help to overcome the ‘ceiling-effect’ that is observed with standard vitamin C.
How does Ester-C Vitamin C compare to other vitamin C supplements?
While other high-strength supplements may deliver 1000mg vitamin C, the chances are that only 15-20% from standard vitamin C supplements will actually be absorbed and retained. Unless vitamin C is retained in the body, it won’t be able to deliver benefits.
Standard vitamin C (ascorbic acid)
We do not absorb or retain a significant amount of vitamin C from standard ascorbic acid supplements.
Standard vitamin C is absorbed fairly well at low doses (up to 200mg), but mega-dosing will not lead to raised blood levels after a certain point. If aiming for high levels, it would be necessary to dose repeatedly throughout day and night. Ester-C, however, can be taken as 1 tablet daily due to superior absorption and 24-hour maintenance in leukocytes.
Due to its structure, standard vitamin C struggles to enter cells so is quickly excreted. Large doses can cause gastrointestinal side effects.
Slow-release vitamin C
Studies do not support significant benefits of slow-release vitamin C over even standard vitamin C.
As vitamin C absorption pathways are quickly saturated, slow-release formulations have been proposed as a method to increase vitamin C uptake from supplements. While studies such as Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) (Salonen et al., 2000) showed a beneficial effect on atherosclerotic progression, pharmacokinetic studies comparing slow-release formulations with standard vitamin C do not appear to support superior uptake and retention of vitamin C.
A single-blinded, 4-week randomised placebo-controlled intervention study (Viscovich et al., 2004) comparing 500mg standard ascorbic acid to 500mg slow-release and placebo reported clinically insignificant pharmacokinetic differences between plain and slow-release formulations of ascorbic acid.
Liposomal vitamin C
Ester-C is superior to liposomal vitamin C in terms of its uptake into and retention in immune cells. Liposomal vitamin C bioavailability studies show disappointing results even with mega doses of 4-5g.
A 2008 pilot study looked at vitamin C levels in blood after a mega dose of 5g standard vs liposomal vitamin C and found no significant difference, possibly as there were only 2 subjects (Hickey et al., 2008).
A 2016 study showed that oral liposomal vitamin C was inferior to intravenous (IV) vitamin C but more bioavailable than standard vitamin C (Davis et al., 2016); however, plasma vitamin C levels did not rise as much as expected when compared to standard vitamin C.
Bioavailability comparison summary
Standard ascorbic acid: regardless of the oral dose (even doses with several grams of vitamin C throughout the day), blood levels will not increase beyond a certain point.
Intravenous vitamin C: Superior in terms of elevating ascorbic acid but not feasible for general health.
Slow-release vitamin C: Mechanistically, a slow-release formula should overcome saturation issues, but this is not reflected in pharmacokinetic studies.
Liposomal: Mechanistically, liposomal delivery should be superior to standard vitamin C. While there are few studies to support increased bioavailability of liposomal vitamin C, these are based on doses of 4-5g, and showed disappointing results.
Ester-C: In vitro and human studies support improved bioavailability of Ester-C over standard vitamin C. Ester-C enhances the retention of vitamin C in leucocytes, meaning the movement of vitamin C out of the plasma and into cells may also help to overcome plasma saturation issues observed with other vitamin C supplements. The naturally occurring vitamin C metabolites in Ester-C are able to deliver their antioxidant benefits across the blood-brain barrier.
Ester-C – in summary
- 10x greater bioavailability
- Efficiently absorbed and retained in cells that need it most
- Provides high cellular vitamin C levels for 24 hours
- 1-a-day, high strength dose
- Non-acidic, gentle on the digestive tract
- Multiple health benefits: antioxidant, reduces fatigue, increases iron absorption, supports the immune system, supports collagen formation for healthy bones, cartilage and blood vessels, and supports normal skin, gums, teeth and the nervous system
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Fay MJ, Verlangieri AJ. Stimulatory action of calcium L-threonate on ascorbic acid uptake by a human T-lymphoma cell line. Life Sci. 1991; 49(19):1377-81.
Fay MJ, Bush MJ, Verlangieri AJ. Effect of cytochalasin B on the uptake of ascorbic acid and glucose by 3T3 fibroblasts: mechanism of impaired ascorbate transport in diabetes.
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Hickey S, Roberts HJ, Miller NJ. Pharmacokinetics of oral vitamin C. J Nutr Environ Med. 2008; 17(3):169–177
Huang J, Agus DB, Winfree CJ, Kiss S, Mack WJ, McTaggart RA, Choudhri TF, Kim LJ, Mocco J, Pinsky DJ, Fox WD, Israel RJ, Boyd TA, Golde DW, Connolly ES Jr. Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke. Proc Natl Acad Sci U S A. 2001 Sep 25; 98(20):11720-4.
Lee JK, Jung SH, Lee SE, Han JH, Jo E, Park HS, Heo KS, Kim D, Park JS, Myung CS. Alleviation of ascorbic acid-induced gastric high acidity by calcium ascorbate in vitro and in vivo. Korean J Physiol Pharmacol. 2018 Jan; 22(1):35-42.
Mitmesser SH, Ye Q, Evans M, Combs M. Determination of plasma and leukocyte vitamin C concentrations in a randomized, double-blind, placebo-controlled trial with Ester-C. SpringerPlus (2016) 5:1161
Moyad MA, Combs MA, Vrablic AS, Velasquez J, Turner B, Bernard S. Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations. Adv Ther. 2008 Oct; 25(10):995-1009.
Salonen JT, Nyyssönen K, Salonen R, Lakka HM, Kaikkonen J, Porkkala-Sarataho E, Voutilainen S, Lakka TA, Rissanen T, Leskinen L, Tuomainen TP, Valkonen VP, Ristonmaa U, Poulsen. Antioxidant supplementation in the Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis. J Intern Med. 2000 Nov; 248(5):377-86.
Viscovich M, Lykkesfeldt J, Poulsen HE. Vitamin C pharmacokinetics of plain and slow release formulations in smokers. Clin Nutr. 2004 Oct; 23(5):1043-50.