As healthcare practitioners, we are well aware of the endless benefits of vitamin C in supporting immune health, antioxidant support, energy production, collagen formation, nervous system function and iron absorption. Faced with a huge array of vitamin C products, however, how can we be confident we’re recommending the best supplement to our clients? During R&D for our latest addition to the Igennus Healthcare Nutrition synergistic range of supplements, we were impressed by both the high absorption of Ester-C and the unprecedented uptake and retention in immune cells. Ester-C boasts an impressive 10x higher bioavailability in leukocytes, whilst its pH neutral composition means it’s also gentle on the stomach. In this webinar, Dr Danielle Crida discusses: - A recap of vitamin C basics - The research that led to the production of Ester-C - The case for  Ester-C: success in clinical use above standard vitamin C supplements - Practical applications and dosing

1. Ester-C® 1400mg
Vitamin C 1000mg
Dr Danielle Crida MBChB, Dip Nutr
Nutritionist, Igennus Healthcare Nutrition
1
Introducing

2. Contents
• Ester-C® formulation
• Ester-C® key features
• Vitamin C background
• Vitamin C insufficiency
• Vitamin C health benefits
• Vitamin C supplementation considerations
• Accumulation and retention in cells
• Comparison to other forms of vitamin C
• Bioavailability comparison summary
• Effect on digestive tract
• Practitioner applications
• Nutritional information

3. Ester-C® is the latest addition to our Synergistic Nutrients
range – products with therapeutic, clinical applications that
are highly effective when used in combination with our clinical
omega-3 range, but are also proven standalone nutrition
supplements with impressive scientific evidence supporting
their use.
Introduction

4. A superior vitamin C formulation
Ester-C® is a unique, patented form of vitamin C that offers superior bioavailability and
duration of action.

5. Features of Ester-C®
Ester-
C®
Optimal
absorption
10x greater
ability to
enter
immune cells
24-hour
action in
immune cells
Stomach
friendly
1-a-day

6.  Vitamin C is a water-soluble micronutrient needed for normal cell function, growth and
development
 Unlike animals, humans lack the enzyme L-gulonolactone and are unable to produce vitamin
C, therefore it must be obtained from diet or supplements
 Standard vitamin C is absorbed fairly well from the gut into the bloodstream at low to medium
doses, but struggles to enter cells and is excreted quite rapidly from the body
 For vitamin C to perform its functions it must act within cells, and Ester-C® Vitamin C’s unique
advantage is that it is 10x more bioavailable to enter immune cells
 It also remains at high levels
in cells for 24 hours
About vitamin C

7. • Fruit and vegetables are the main sources, e.g. citrus fruit, kiwi, mango,
broccoli, tomatoes and peppers
• Current Reference Intake is 80mg/day
• Smokers require 35mg additional vitamin C/day
• 5-9 servings of fresh or frozen fruit and vegetables provides ~200mg of
vitamin C
Vitamin C sources
REGULATION (EU) No 1169/2011 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 25 October 2011 on the provision of food information to
consumers. (22.11.2001) Official Journal of the European Union. L 304/18

8. • Reduced intake
– Low fruit and veg intake, cooking methods, storage etc
• Increased requirements
– Pregnancy
• Reduced absorption
– Sodium vitamin C transporters SNPs (genetic
predisposition)
– Inflammatory bowel disorders
• Increased oxidative stress
– Smoking, strenuous exercise
• Underlying health conditions
– e.g. diabetes, hypertension, obesity
Sufficiency
Deficiency
Insufficiency
Factors relating to vitamin C deficiency

9. • Fatigue
• Poor immunity
• Poor wound healing
• Gum inflammation and bleeding
• Abnormal bruising and bleeding
• Muscle, joint and back aches
• Skin disorders:
very dry skin, follicular hyperkeratosis
Deficiency of vitamin C is linked to various disorders and systems

10. Multiple health benefits of vitamin C

11. • Accumulation
and retention in cells
• Ester-C® vs other
vitamin C formulations
• Bioavailability comparison summary
• Effects on digestive tract
Vitamin C supplementation
considerations

12. Accumulation and retention in cells
• Ester-C® contains threonate, a vitamin C metabolite
• Threonate and other vitamin C metabolites
act by preventing/reducing extracellular oxidation
and metabolism of vitamin C, and/or enhancing
the active transport of vitamin C into cells
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.

13. Accumulation and retention in cells cont ...
• Ester-C® contains calcium ascorbate, which has been shown
to significantly increase vitamin C accumulation in leucocytes, which are key players
in immunity
• Vitamin C levels remain high at 24 hours, supporting 1-a-day dosing
Mitmesser S, 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
10x greater AUC for the accumulation within leukocytes of Ester-C ® vs ascorbic acid

14. Ester-C® vs. liposomal vitamin C
•Human studies of liposomal vitamin C are lacking
•While the concept and use of liposomes for pharmaceutical delivery
are well established, there is currently insufficient data to suggest
benefits over standard ascorbic acid
•Unlike Ester-C® , liposomal Vit C is not optimally absorbed into cells,
and is quickly excreted from the body
•Ester-C® is also more cost effective
than liposomal vitamin C
•For these reasons, we conclude that
Ester-C® is superior to
liposomal vitamin C
Ester-C® vs other vitamin C formulations

15. Slow release vitamin C
•Pharmacokinetic studies comparing slow release formulations with
standard vitamin C do not support statistically significant superior
uptake and retention of vitamin C from slow release formulations
•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.
Ester-C ® vs other vitamin C formulations

16. Effects on the digestive tract
• Ingestion of high doses of vitamin C can cause gastrointestinal
distress: abdominal cramps, nausea and diarrhoea
• N=50 healthy volunteers sensitive to acidic foods
• Double-blind, crossover study
• Ester-C® 1000mg or ascorbic acid 1000mg
• Medication for 3 days, 3 day washout, other medication for 3 days
• Statistically significant fewer epigastric adverse events
• 72% rated tolerability of Ester-C® as ‘very good’
• Ester-C® Vitamin C is buffered and
pH neutral, so gentle on the digestive
tract, even in high doses
•Gruenwald J, Graubaum HJ, Busch R, Bentley C.
Safety and tolerance of ester-C compared with regular ascorbic acid.
Adv Ther. 2006 Jan-Feb;23(1):171-8.

17. Practical applications
Which clients are recommended Ester-C® ?
• Immune system support: prevention and treatment of
common cold and pneumonia
• Dental disease - e.g. gingivitis, periodontal disease
• Wound healing – post-operative/trauma
• Athletes
• Skin conditions - e.g. keratosis pilaris, dry skin
• Joint pain
• Fatigue
• Anaemia - iron absorption

18. Ester-C® and the common cold
• n=168, non-influenza vaccinated. Double-blind, placebo-controlled trial
• Ester-C® 1000mg or placebo once daily for 60 days btwn Nov and Feb
• Well tolerated, greatly increased satisfaction vs previous vit C supplements
• Active treatment group had significantly fewer colds (37 vs 50, P<.05), and
• Fewer days challenged virally (85 vs 178)
• Significantly shorter duration of severe symptoms (1.8 vs 3.1 days, P<.03)
• During the study, 16 in placebo group experienced more than one full-blown cold; only 2 volunteers in active group had a
reinfection
• 77% reduction in coughing compared to previous winters
• 85% of respondents in the active group would continue taking the compound, and 81% would recommend it to friends and
family. 64% of the active group felt “better” or “much better” during the trial
Volunteers in the active group
were less likely to get a cold
and recovered faster if infected
Van Straten,M Josling,P Preventing the Common Cold With a Vitamin C
Supplement: A Double-Blind, Placebo-Controlled Survey. Advances in Therapy
Vol 19 No.3 May/June 2002

19. Vitamin C and immune function –
review article
Vitamin C contributes to immune function by:
• Supporting various cellular functions of both the innate
and adaptive immune system
• Supports epithelial barrier function against pathogens
• Promotes oxidant scavenging activity of the skin,
potentially protecting against oxidative stress
• Accumulating in phagocytic cells, e.g. neutrophils, to enhance
chemotaxis, phagocytosis, generation of ROS and
ultimately microbial killing
• Needed for apoptosis and clearance of spent neutrophils from
sites of infection by macrophages, thereby decreasing necrosis
and potential tissue damage
• In lymphocytes: enhance differentiation and proliferation
of B and T cells
Anitra C. Carr 1,* and Silvia Maggini Vitamin C and Immune Function November
2017 Nutrients 2017, 9, 1211; doi:10.3390/nu9111211

20. Vitamin C and immune function -
a review article
• Vitamin C supplementation is able to both
prevent and treat respiratory and systemic infections
• Meta-analysis indicates vitamin C 200 mg or more daily decreases the severity and
duration of the common cold, and the incidence of the common cold if also exposed
to physical stress. Supplementation of individuals who had an inadequate vitamin C status
(i.e. 45 µmol/L) also decreased the incidence of the common cold
• In contrast, treatment of established infections requires significantly higher doses of the vitamin to
compensate for the increased inflammatory response and metabolic demand
• Prophylactic vitamin C decreases the risk of serious respiratory infections - e.g. pneumonia
• Beneficial effects of vitamin C on recovery have been noted in pneumonia
Higher doses (0.5–1.6 g/day) reduced the duration by 36%
Carr,A. and Maggini,S. Vitamin C and Immune Function Nutrients Nov 2017, 9, 1211; doi:10.3390/nu9111211

21. Osteoarthritis
Reduced pain from osteoarthritis in hip and knee joints during treatment
with calcium ascorbate
A randomised, placebo-controlled cross-over trial in general practice
• N=133, radiologically verified symptomatic OA of hip/knee joints
• Multicentre, double-blind performed by ten general practitioners
• 1000mg calcium ascorbate/placebo; 14 days each separated by 14 day washout
• Calcium ascorbate reduced pain significantly compared to placebo (p = 0.0078)
• The demonstrated effect is less than half as pronounced as commonly reported for NSAID
Jensen NH Reduced pain from osteoarthritis in hip joint or knee joint during treatment with calcium ascorbate. A randomised, placebo-controlled cross-
over trial in general practice Ugeskr Laeger. 2003 Jun 16;165(25):2563-6

22. Vitamin C
in skin disease
Roles of vitamin C:
• Promotes collagen synthesis
• Antioxidant
• Increases other antioxidant levels
by altered gene expression
• Differentiation of keratinocytes
• Enhanced barrier function due to increased barrier lipids, improved organisation of
stratum corneum
• Wound healing – increases proliferation and migration of dermal fibroblasts
• Increases glycosaminoglycan (GAG) synthesis
Pullar, J. M., Carr, A. C., & Vissers, M. (2017). The Roles of Vitamin C in Skin Health. Nutrients, 9(8), 866. doi:10.3390/nu9080866

23. Vitamin C deficiency: skin signs and symptoms
• Poor wound healing
• Rough skin: thickening of stratum corneum
• Dry skin: loss of barrier lipids and barrier function
• Subcutaneous bleeding (fragility, loss of connective tissue)
• Corkscrew hairs
• Scurvy: skin fragility, bleeding gums, corkscrew hairs, impaired wound
healing
• Changes extreme and rapid in onset in vitamin C-deficient
individuals
• Similar processes occur when body stores are
below optimal, although to a lesser extent
• Pullar, J. M., Carr, A. C., & Vissers, M. (2017). The Roles of Vitamin C in Skin Health.
Nutrients, 9(8), 866. doi:10.3390/nu9080866

24. Skin: vitamin C supplementation –
topical or systemic ?
• Dermal layers best supported by nutrients delivered
through the bloodstream
• Vitamin C uptake from the bloodstream and transport across the skin layers is
mediated by specific sodium-dependent vitamin C transporters (SVCTs)
• Epidermis challenged environment for nutrient delivery – lacks blood vessels,
relies on diffusion from dermis. Outer epidermial layers: little movement of
extracellular fluid between cells due to the complex lipid/protein crosslink
structure forming the skin barrier
• If plasma levels saturated, then it appears that topical application does not
increase skin vitamin C content
• Topical applications unlikely to reach dermis
Pullar, J. M., Carr, A. C., & Vissers, M. (2017). The Roles of Vitamin C in Skin Health.
Nutrients, 9(8), 866. doi:10.3390/nu9080866

25. Type of skin damage Skin structure affected Evidence of effect – Vitamin
C
Sunburn Cell death of all skin cells,
with associated inflammation
Improved skin vit C level
improves resistance to UV
exposure
Wrinkle formation Dermal layer changes,
deterioration of collagen and
elastic fibres
Lessening of wrinkle depth
following vitamin C
supplementation. Increased
collagen formation by
fibroblasts in cell culture
Dry and rough skin Stratum corneum: loss of skin
barrier lipids and natural
moisturising factor
Vitamin C enhances
production of barrier lipids in
cell culture
Excessive scarring, keloid
formation
Abnormal fibroblast function,
collagen and elastin
formation
Vitamin C improves wound
healing, prevents keloid
formation
Table: Skin ailments, their causes and evidence from in vitro and in vivo studies for association with vitamin C levels.
Pullar, J. M., Carr, A. C., & Vissers, M. (2017). The Roles of Vitamin C in Skin Health. Nutrients, 9(8), 866. doi:10.3390/nu9080866

26. Periodontal disease
Possible connections between periodontal disease and:
• Atherosclerosis & heart disease — May increase the risk of,
and worsen existing heart disease
• Stroke — May increase the risk of ischaemic stroke
• Diabetes — May worsen blood glucose control
• Respiratory disease— May cause lung infections and worsen
existing lung conditions when bacteria from the mouth reach the lungs
Java project on periodontal diseases: effect of vitamin C/calcium threonate/citrus flavonoids
supplementation on periodontal pathogens, CRP and HbA1c
• N=98 periodontally diseased, rural population : poor diet, lack of dental care
• One tablet/day containing 200 mg Ester-C® calcium ascorbate, 25 mg calcium threonate and 100 mg citrus
flavonoids for 90 days
• 100% of subjects showed normal plasma vitamin C values compared to 55% before
• Reduced subgingival load of all studied periodontal pathogenic bacteria (p-values: 0.014-0.0001) and
Epstein Barr Virus (p < 0.0001)
• Plasma levels of HbA1c and hsCRP dropped in all subjects (p < 0.0001)
Amaliya A, Laine ML, Loos BG, Van der Velden U Java project on periodontal diseases: effect of vitamin C/calcium
threonate/citrusflavonoidssupplementation on periodontal pathogens, CRP and HbA1c. J Clin Periodontol. 2015 Dec;42(12):1097-104. doi:
10.1111/jcpe.12478. Epub 2015 Dec 21
Periodontal
disease
Systemic
illness

27. Reduced risk of kidney stones:
Ester-C® vs ascorbic acid
• One of the causes of hyperoxaluria (a risk factor for kidney stones) is high dose (>1000mg/day) vitamin C supplementation
• Randomised, double blind, crossover study
• N=50; Given Ester-C® followed by ascorbic acid or vice versa
• 5 days: 1000mg vitamin C/day, 5 days 2000mg vitamin C/day
• 7 day washout, repeated with other form of vitamin C
• Significant change in 24-hour urine oxalate levels comparing the two treatments (p = 0.04)
• Decrease of urine oxalate levels in the Ester-C® group
• Increase in urine oxalate in the ascorbic acid group
Moyad MA1, Combs MA, Crowley DC, Baisley JE, Sharma P, Vrablic AS, Evans M. Vitamin C with metabolites reduce oxalate levels compared to ascorbic
acid: a preliminary and novel clinical urologic finding. 2009 Society of Urologic Nurses and Associates U rologic Nurs i n g , p p . 9 5 - 1 0 2 .
Ester-C® Ascorbic acid
24-hour urine oxalate (umol/day )
Baseline 305 300
10 days 282 315

28. Vitamin C and iron absorption
• Iron deficiency common in overweight and obese women
Adipose tissue and liver produce hepcidin = master regulator of iron metabolism
Hepcidin secretion increased by subclinical inflammation
Hepcidin decreases absorption of iron from gut and decreases iron flow from bloodstream into cells
• N=64 healthy, non-anaemic women
• Conclusions: In overweight and obese women, iron absorption is two-thirds that in normal-weight women, and the
enhancing effect of ascorbic acid on iron absorption is one-half of that in normal-weight women. Recommending
higher intakes of ascorbic acid (or other luminal enhancers of iron absorption) in obese individuals to improve iron
status may have a limited effect.
• Ana C Cepeda-Lopez Alida Melse-Boonstra Michael B ZimmermannIsabelle Herter-Aeberli, In overweight and obese women, dietary iron
absorption is reduced and the enhancement of iron absorption by ascorbic acid is one-half that in normal-weight women The American
Journal of Clinical Nutrition, Volume 102, Issue 6, 1 December 2015, Pages 1389–1397, https://doi.org/10.3945/ajcn.114.099218
Normal weight
women
Overweight/obese
women
Iron absorption: Meal
without vitamin C
19% 12,9%
Iron absorption: Meal
with vitamin C
29.5% 16,6%
Median percentage
increase in
absorption
56% 28%

29. • Adults: 1 tablet daily
Exceeding recommended dose
• no tolerable upper limit for vitamin C
• >1g/day limited additional benefit,
with potential side effects
Children
• Age 8 years and over:
half tablet daily
• Break line for easy halving
Scientific Committee on Food ;Scientific Panel on Dietetic Products,
Nutrition and Allergies.(Feb 2006)Tolerable Upper Intake Levels for
Vitamin and Minerals. European Food Safety Authority
Dosing advice

30. • Swallowing difficulties – halve along break line
• Similar time each day, ideally with food
Dosing advice

31. • GETS INTO CELLS, WHERE YOU NEED IT MOST:
Whereas standard vitamin C struggles to enter cells,
Ester-C®’s vitamin C metabolites ensure 10x greater
absorption
• 1-A-DAY CONVENIENCE: 1 tablet daily ensures
high level in cells for 24 hours
• HIGH-STRENGTH DOSE
Ester-C® 1400mg, vitamin C 1000mg
• STOMACH-FRIENDLY: Buffered, non-acidic formula
is gentle on the digestive tract
• MULTIPLE HEALTH BENEFITS: Vitamin C is an
antioxidant, reduces tiredness, increases iron
absorption, supports the immune system, supports
collagen formation for healthy bones, cartilage &
blood vessels, and supports normal skin, gums,
teeth and the nervous system
• CONSISTENT PRODUCT QUALITY
GUARANTEED: manufactured in the UK in GMP-
accredited facilities
Features of Ester-C® Vitamin C

32. Nutritional information
Warnings
This product should not be used as
a substitute for a balanced diet.
Pregnant or breastfeeding women
should consult their doctor before
taking any food supplement. Keep
out of reach of children and store in
a cool, dry place away from direct
sunlight.
*% Reference Intake
Serving size:
1 tablet
Per
serving
% RI*
Ester-C®
(as Ester-C® Calcium
Ascorbate-Threonate)
of which Vitamin C
1400mg
1000mg
n/a
1250%

33. Commercial Technical Nutrition advice
Mina Nazemi
Commercial Director
minan@igennus.com
Dr Nina Bailey
Head of R&D
ninab@igennus.com
Danielle Crida
Nutritionist
danielle@igennus.com
Contact