Igennus are excited to announce the launch of our new product, Longvida® Curcumin. During this webinar, Dr Bailey reviews the research behind the therapeutic use of curcumin and why Longvida is the world’s most advanced formulation of the nutrient. Curcumin is a polyphenol compound obtained from the rhizome of Curcuma longa, also known as turmeric. This Indian spice has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Curcumin is well documented for its antioxidant, anti-inflammatory and anti-cancer activities. Although it has been shown to be safe at high doses (12g/d), it is poorly absorbed, undergoes rapid intestinal and hepatic metabolism and is rapidly eliminated from the body. As such, standard curcumin demonstrates poor bioavailability, even at high doses, limiting its therapeutic potential. After much research and discussion (it’s a big and complicated topic!) between the Igennus nutrition scientists, the decision as to which type of curcumin we would use for our Synergistic Nutrients range was actually a very straightforward one. Longvida Curcumin utilises a novel delivery system (SLCP), which protects curcumin from the harsh environment of the stomach and promotes its rapid absorption into the bloodstream and target tissues, even at low doses – resulting in an incredible 285x superior bioavaibility compared with standard curcumin, 65x higher peak plasma levels and 7x longer-lasting action. Longvida is the only formulation proven to deliver high levels of free form, unconjugated curcumin, into the bloodstream. Free form curcumin is the form required for therapeutic benefits, and the only form proven to cross the blood brain barrier. This webinar covers: - What curcumin is, what it does and how? - Why free form curcumin is essential for therapeutic effects - The research and current evidence for Longvida Curcumin’s unique health benefits - How Longvida overcomes significant bioavailability issues associated with curcumin use - To who, why and when you should recommend curcumin …and more.

1. Curcumin
Nina Bailey BSc MSc, PhD RNutr
1

2. Curcumin is a polyphenolic molecule extracted from the rhizome of the
plant Curcuma longa, a yellow spice most commonly encountered as a traditional
ingredient of curry
This natural compound has been used over centuries in Ayurvedic, Chinese and Hindu
traditional medicine to treat a number of both minor and chronic conditions
Numerous studies have demonstrated that curcumin possesses anti-oxidant, anti-
inflammatory and anti-cancer properties

3.  Turmeric contains an average of 5-10% curcuminoids
 Curcumin (75%)
 Demethoxycurcumin (DMC -15%)
 Bis-demethoxycurcumin (BDMC – 10%)
 Other components include:
 Volatile (essential) oils 3-7%; fibre 2-7%; mineral matter 3-7%; protein 6-8% fat
5-10%; moisture 6-13% & carbohydrates 60-70%
 Average intake (India) is as much as 2-3g daily

4. From traditional medicine to modern medicine
• Since the time of Ayurveda (around 1900 BC) numerous therapeutic activities have
been ascribed to turmeric for a wide variety of diseases and conditions
• Extensive research within the last half century has proven that most of these
activities, once associated with turmeric, are due to curcumin with its structure as
only determined in 1910
• Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral,
antibacterial, antifungal and anticancer activities and thus has potential against
various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and
other chronic illnesses
• The first study on curcumin’s biological activity (according to Pubmed) as an
antibacterial agent was published in 1949 in Nature and the first clinical trial was
reported in The Lancet in 1937
• Although the current database indicates almost 10,000 publications on curcumin,
until 1990 there were less than 100 papers published

5. Curcumin mechanisms
• Inflammation and pro-inflammatory processes are centrally linked to several chronic human
diseases, including cancer, diabetes, obesity, arthritis, and cardiovascular and neurodegenerative
diseases
• In in vitro, animal and human studies, curcumin has shown antioxidant, anti-cancer, anti-tumour,
anti-arthritic, anti-amyloid, anti-ischemic and anti-inflammatory properties, as well as other
benefits
• Curcumin’s multitude of health benefits are primarily (but not exclusively) attributed to its direct
targeting of the transcription factor nuclear factor kappa B ( NF-κB ), also known as the
inflammatory ‘master switch’
• When NF-κB is stimulated (by factors such as stress,
inflammation, pathogens, lipopolysaccharides (LPS),
trauma and so on), it is released from its inhibitory
molecule IKB, thereby allowing its movement to the cell
nucleus where it ‘switches on’ genes responsible for the
production of a number of proinflammatory products,
initiating an inflammatory cascade of events
• Curcumin prevents NF-κB from entering the nucleus,
thereby blocking inflammation at an early stage

6. NF-κB in chronic disease – a target for
nutritional intervention

7. Curcumin can modulate various types of signalling molecules including transcription
factors, enzymes, growth factors, interleukins, cytokines & chemokines
Ghosh S, Banerjee S, Sil PC. The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update. Food Chem Toxicol. 2015 Sep;83:111-24.

8. Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M Curcumin and Health. Molecules. 2016 Feb 25;21(3):264.
Antioxidant properties and reactive oxygen species (ROS)
scavenger effects of curcumin

9. Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP. Pharmacodynamic and pharmacokinetic study of oral Curcuma
extract in patients with colorectal cancer. Clin Cancer Res. 2001;7:1894–1900
Wahlstrom B, Blennow G. A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol (Copenh) 1978;43:86–92.
•As curcumin has poor aqueous solubility, very little gets into the circulation and simply passes
through the body via the gastrointestinal system
•In contrast, any curcumin that is absorbed undergoes extensive first-pass metabolism
optimising its efficient excretion by the kidneys - thus, the majority of oral curcumin is simply
excreted
•High doses of curcumin (>400 mg/kg of body weight) are required to obtain detectable tissue
levels in rats
 Wahlstrom et al (1978) administered curcumin at 1 g/kg to Sprague-Dawley rats and found 65–85% of
the dose excreted unchanged in the faeces, with negligible amounts in the urine
 Sharma et al (2001) administered Curcuma extract 440 to 2,200 mg/day (36 to 180 mg of curcumin) for
up to 29 days to patients with advanced colorectal cancer and failed to detect curcumin or its
metabolites in blood or urine, with considerable amounts found unchanged in the faeces
For curcumin supplements to offer significant health benefits steps must be taken to
increase absorption and prevent excretion
Curcumin's benefits are hampered by its poor bioavailability

10. Free curcumin vs. glucuronidated curcumin
Curcumin is a lipophilic molecule that is nearly insoluble in water and the process of
glucuronidation and sulfation (by the intestines and liver) renders curcumin water soluble,
thereby allowing its efficient excretion via the kidneys
– Curcumin’s major metabolites are the glucuronides
of tetrahydrocurcumin (THC) and hexahydrocurcumin
(HHC) both of which are significantly less active
than curcumin in the free form
– Free, unconjugated (unmetabolised) curcumin is,
by nature, less water soluble, and therefore present
for longer in the body
The focus on increasing curcumin’s bioavailability is to optimise solubility, stability,
permeability and to deliver curcumin to target tissues in the free form
Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M Curcumin and Health. Molecules. 2016 Feb 25;21(3):264.

11. • Patients (n-25) received 8 g curcumin (900 mg curcumin, 80 mg DSM and 20 mg
BDSM) for 8 weeks
• Circulating curcumin was detectable as well as glucuronide and sulfate conjugate
forms, suggesting poor oral bioavailability
• Curcumin down-regulated expression of NF-kB and COX-2
• Curcumin levels peaked at 22 to 41 ng/mL with considerable inter-patient
variation
The study concluded that a high dose of oral curcumin is well-tolerated and, despite
limited absorption, has some biological activity in some patients with pancreatic
cancer
Overcoming biovaiaibility issues would allow smaller doses to be delivered in clinical
settings
Phase II Trial of curcumin in patients with advanced pancreatic
Cancer

12.  Potent antioxidant effects– curcumin’s antioxidant mechanisms protect cells against oxidative
damage
 Improves liver function – curcumin regulates the activity of a number of key enzymes and
antioxidants essential for optimal detoxification
 Cardiovascular health – curcumin promotes cardiovascular health and function, and protects
low density lipoprotein (LDL) from oxidation
 Immune health – curcumin improves and supports immune function
 Joint health – curcumin significantly improves
joint health by reducing inflammation and
promoting joint comfort and flexibility
 Digestive health – curcumin stimulates bile
production and promotes healthy digestive
function
 Anti-cancer benefits – curcumin offers protective
benefits against the main hallmarks of cancer
including angiogenesis, proliferation, metastasis,
inflammation and apoptosis
NF-κB in chronic disease – a target for nutritional intervention

13. Curcumin bioavailability is dependent on a number of factors
• Solubility - curcumin must be able to ‘dissolve’ into the contents of the
stomach - if it isn’t soluble, it won’t be absorbed
• Stability - curcumin is a very delicate compound that must be able to
survive harsh acidic or alkaline conditions as well as glucuronidating
enzymes
• Permeability - curcumin must get across the cells of the stomach or
intestines and into the system to have an effect on the body’s target
tissues (and to pass the blood-brain barrier to have cognitive benefits)
• Metabolism – curcumin must avoid metabolism by enzymes present in the
lining of the gut and, to a greater extent, in the liver – the metabolites of
curcumin are not in an active form and are easily excreted

14. Heal t h benef i t s
If bioavailability is
optimised, meaning
that free form
curcumin reaches
therapeutic levels in
plasma which are
active for a
sufficient length of
time, the health
benefits of
curcumin are many!

15. Use of piperine to increase the bioavailability of
curcumin
Piperine is a compound commonly found in black pepper known to slow down hepatic and
intestinal glucuronidation, which basically means elimination of different substances from the liver
and gut
This is helpful in increasing the bioavailability of curcumin because it stays in the body longer and
higher levels of curcumin get past the liver and stomach
•In humans (n=6), serum levels curcumin were either undetectable or very low after a dose of 2g
•Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to
1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), with an increase in bioavailability of
2000%
•Piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in
humans with no adverse effects
But……is blocking glucuronidation necessarily a good thing?
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human
volunteers. Planta Med. 1998 May;64(4):353-6.

16. Kidneys
Molecules excreted via
urine
Gallbladder
Heavier molecules are mixed with
bile and eliminated in the faeces
Processed toxins ready
for elimination
Phase II Detoxification
Conjugation makes molecules more
water soluble for easy elimination
Phase I Detoxification
Oxidise, reduce or hydrolyse toxins, to
break them into smaller, electrically-
charged substances
Intermediate
metabolites
Superoxide
radicals
Radical oxygen
intermediates
Microbial endotoxins
Metabolic byproducts
Drugs & chemicals
Secondary tissue
damage

17.  To improve the bioavailability of curcumin, numerous approaches have been
undertaken, including:
• Use of adjuvant that interferes with glucuronidation
 Piperine (black pepper extract)
• Inclusion of turmeric volatile oils
 BCM-95®
• Nanoformulations (liposomes, micelles, etc)
 Novasol®
 Longvida®
 Curcuwin
• The use of curcumin phospholipid complex
 Meriva-SR®
 Micelles and phospholipid complexes increase the absorption resulting
in higher blood plasma concentration and lower elimination, thus
increasing the bioavailability. Of these Meriva-SR® and Longvida®
have
shown promise in human clinical trials

18. Meriva vs. Longvida

19. Phytosome technology
Meriva (phospholipid complex)
Natural curcuminoid mixture (20%)
•75% curcumin
•15% DMC
•10% BDMC
Phosphatidylcholine (40%)
Microcrystalline cellulose (40%)
Phytosomes are more bioavailable than
uncomplexed curcuminoids due to their
enhanced capacity to cross the lipid
membranes and to reach the systemic
circulation
Phospholipid
Curcuminoid
Curcuminoid-
phospholipid complex

20. Marczylo TH, Verschoyle RD, Cooke DN, Morazzoni P, Steward WP, Gescher AJ. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer
Chemother Pharmacol. 2007 Jul;60(2):171-7. Epub 2006 Oct 19.
Meriva vs. standard curcumin (rodents)
These results indicate that whilst Meriva’s Phytosome technology increases the bioavailability
of curcuminoids it doesn’t reduce phase II glucuronidation processes – we need to focus on
raising free curcumin
• Rats received 340 mg/kg of either unformulated curcumin or curcumin formulated with
phosphatidylcholine (Meriva)
• Peak plasma levels and area under the plasma concentration time curve (AUC) values for parent
curcumin after administration of Meriva were fivefold higher (26.7 vs 4.8 mg min/ml) than the
equivalent values seen after unformulated curcumin
• Liver levels of curcumin and curcumin metabolites were higher after administration of Meriva
as compared to unformulated curcumin
Cmax (nM) Tmax (min) AUC (mg min/ml)
Standard curcumin
Free curcumin 6.5 ± 4.5 30 4.8
Curcumin glucoronidate 225 ± 0.6 30 200.7
Curcumin sulphate 7 ± 11.5 60 15.5
Meriva Phytosome
Free curcumin 33.4 ± 7.1 15 26.7
Curcumin glucuronidate 4,420 ± 292 30 4,764.7
Curcumin sulphate 21.2± 3.9 60 24.4

21. Meriva vs. standard curcumin (human study)
Cuomo J, Appendino G, Dern AS, Schneider E, McKinnon TP, Brown MJ, Togni S, Dixon BM. Comparative absorption of a standardized curcuminoid
mixture and its lecithin formulation. J Nat Prod. 2011 Apr 25;74(4):664-9. doi: 10.1021/np1007262. Epub 2011 Mar 17.
• A randomised, double-blind, crossover study was carried out in nine volunteers, measuring the
plasma concentrations of three curcuminoids [curcumin, DMC and BDMC] after supplementation
with two dosages of Meriva and one dosage of the same batch of standard curcumin
• Doses were based on clinical studies for inflammatory conditions, where active dosages of around 1-2
g/day of standard curcumin - around 200-300 mg of curcuminoids as Meriva were used
• Subjects consumed, in random order and on separate study days, five (low-dose) or nine (high-dose)
capsules of Meriva, corresponding to 209 and 376 mg total curcuminoids, or, alternatively, five
capsules of the corresponding non-formulated curcuminoid mixture (reference) containing 1799 mg
of total curcuminoids
• Both materials had a similar ratio of all three natural curcuminoids (75% curcumin, 15% DMC, 10%
BDMC)
Meriva High dose Meriva Low dose Reference dose
Free curcumin 297 165 1295
DMC 68 38 369
BDMC 11 6 108
Total curcuminoids 376 209 1799

22. Meriva vs. standard curcumin (human study)
Cuomo J, Appendino G, Dern AS, Schneider E, McKinnon TP, Brown MJ, Togni S, Dixon BM. Comparative absorption of a standardized curcuminoid
mixture and its lecithin formulation. J Nat Prod. 2011 Apr 25;74(4):664-9. doi: 10.1021/np1007262. Epub 2011 Mar 17.
Cmax (ng/mL) Tmax (h) AUC (ng/mL)
Meriva high dose
Free curcumin 50 ± 13 3.8 538 ± 131
DMC 135 ± 41 2.4 655 ± 196
BDMC 25 ±8 2.2 142 ± 58
Total curcuminoids 207 ± 55 2.7 1136 ± 357
Meriva low dose
Free curcumin 24 ± 6 4.2 272 ± 68.52
DMC 39 ± 11 3.1 297 ± 107
BDMC 9 ± 3 2.4 70 ± 34
Total curcuminoids 69 ± 17 3.3 640 ± 198
Reference
Free curcumin 9 ± 3 6.9 123 ± 29
DMC 4 ± 1 4.4 56 ± 16
BDMC 2 ± 0.8 3.4 25 ± 10
Total curcuminoids 14 ± 4 6.9 203 ± 54
• Phytosome delivered curcuminoids (209 mg
and 376 mg) resulted in significantly higher
plasma levels than a higher dose of
unformulated curcuminoids (1799 mg)
• However, the major plasma curcuminoid
‘delivered’ by Meriva was DMC and not
curcumin
• The marked differences in the plasma
curcuminoid profile could not be accounted
for by the nature of the starting materials,
since Meriva capsules and the noncomplexed
curcumin capsules contained very similar
curcuminoid profiles
• The DMC & BDMC forms of curcumin were therefore absorbed better than free curcumin
• No information on curcumin metabolites (curcumin glucuronidate or sulphate) provided
Curcumin, the principal curcuminoid found in turmeric, is generally considered its most active constituent

23. Longvida technology
• Solid Lipid Curcumin Particle
technology (SLCP) is a novel process
based on supercritical fluid
technology used for encapsulating
curcumin in solid lipid particles (SLP)
to yield curcumin formulations with
enhanced and superior properties
• Longvida uses supercritical fluid (SCF) technology which operates under
mild conditions, avoids high temperatures (curcumin is heat sensitive)
and, unlike many competitor products, is also free of harsh solvents and
volatile oils, and piperine (which blocks the glucuronidation of curcumin
but can also therefore interfere with other essential glucuronidation
involved in phase II liver detoxification processes)

24. Longvida optimized curcumin delivery system
 Longvida curcumin is able to survive the harsh digestive pH conditions and
doesn’t get destroyed by the acidic environment of the stomach
 Longvida provides a unique coating (of highly purified fatty acids and
phospholipids) that surrounds the curcumin molecule and enables it to be
transported into the lymphatic system rather than the circulatory system
 Unlike the circulatory system, the lymphatic system bypasses the liver
(the major organ for metabolism) so less curcumin is exposed to
metabolic enzymes and remains in a free form
 The small particle size of
Longvida curcumin
ensures its easy passage
across the intestinal cell
membrane

25. Longvida vs. standard curcumin (human study)
650 mg Longvida
curcumin
650 mg standard
curcuminoids
Cmax (ng/mL) 22.43 ± 1.92 <1
Tmax (hours) 2.4 ± 0.44 na
AUC (0-t) (ng/mL-h) 95.26 ± 4.62 na
T ½ (h) 7.46 ± 2.43 na
• Healthy subjects (n=6) were given Longvida or 95% curcuminoids extract (standard curcumin) at a
dose of 650 mg
• 400 mg Longvida® Optimized Curcumin,
contains approximately 80 mg curcumin
in a solid lipid formulation so the dose of
650mg equates to approximately 130
mg curcumin
• Plasma concentrations of curcumin were
significantly higher for Longvida Cmax
(22ng/mL) compared to standard
curcumin (<1ng/mL) - remember –
209mg Mervia curcumin resulted in a
Cmax 24ng/ (24ng/mL)
• Half life was 7.46 hours
• The tmax (time at which the maximum
concentration [Cmax] is observed) was 2.4
hours
Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG: Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. Journal of agricultural and
food chemistry 2010, 58:2095-2099.
Shah et al. Acute human pharmacokinetics of a lipid-dissolved turmeric extract. Planta Med 2012; 78 DOI: 10.1055/s-0032-1320664

26. • Longvida® curcumin is highly stable and highly soluble, optimised to deliver free
curcumin (the active form that is not metabolised or glucuronidated) into the
bloodstream and target tissues
• Free curcumin is the only form that is proven to pass the blood-brain barrier -
curcumin's symmetrical phenol groups make it more brain-permeable and able
to cross the blood-brain barrier
• The concentrations of curcumin detected after dosing with 400mg (80mg
curcuminoids) are in the range offering therapeutic impact in various models
• Longvida® Optimised Curcumin has a patented lipid delivery technology offering
285x greater bioavailability, 65x higher peak plasma levels and 7x longer-lasting
action than standard curcumin
Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG: Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy
volunteers. Journal of agricultural and food chemistry 2010, 58:2095-2099.
Shah et al. Acute human pharmacokinetics of a lipid-dissolved turmeric extract. Planta Med 2012; 78 DOI: 10.1055/s-0032-1320664
Longvida® Optimised Curcumin offers unprecedented bioavailability

27. Longvida curcumin reduces NF-κB transcriptional activity
(and reduces inflammation)
 Longvida curcumin significantly
inhibited the transcriptional activity of
NF-κB in LPS-activated macrophages at
tested concentrations
NF-κB signalling pathway is the predominant upstream molecular signalling pathway that causes
inflammation through enhanced cytokine, nitric oxide and prostaglandin production
Lipopolysaccharides (LPS) are endotoxins found in the outer membrane of Gram-negative
bacteria, and elicit strong immune responses via NF-κB activation
LPS-induced NF-κB up-regulation accounts for a part of LPS-mediated activation of a variety of
inflammatory genes
An in-vitro study to determine the dose effects of Longvida curcumin SLCP formulations on NF-
κB activation in macrophages stimulated with LPS
Nahar PP, Slitt AL, Seeram NP. Anti-Inflammatory Effects of Novel Standardized Solid Lipid Curcumin Formulations. J Med Food. 2015 Jul;18(7):786-92

28. Placebo controlled trial showed supplementation with Longvida curcumin (400 mg/day) to
significantly reduce pro-inflammatory markers of exercise-induced muscle damage
including pro-inflammatory cytokines (IL-6, IL-8, IL-10, and TNF-α) and creatine kinase (CK)
Takahashi M et al., Effects of curcumin supplementation on exercise-induced oxidative stress in humans.
Int J Sports Med. 2014 Jun;35(6):469-75.
Anti-inflammatory effects of Longvida curcumin
PRE
Day 1
Day 2
Day 3
Day 4
PRE
Day 1
Day 2
Day 3
Day 4
Measurements were made prior to (PRE), 1, 2, 3 and
4 days following exercise-induced muscle damage
Heat map for global changes demonstrates that
curcumin treatment was associated with a muted
response for serum cytokines (IL-6, IL-8, IL-10, and TNF-
α) and creatine kinase (CK)
Reduced muscle soreness experienced with curcumin
treatment matches with the pro-inflammatory
biomarkers, particularly at 2 and 4 days

29. The health promoting effects of Longvida curcumin in healthy individuals
Longvida curcumin Lowered
 β-amyloid protein: a marker of brain ageing, especially in relation to
Alzheimer’s disease
 Lowered triglycerides: related to increased risk of poor cardiovascular
health
 Soluble intercellular adhesion molecule (sICAM): linked to
atherosclerosis
 Salivary amylase: a marker of sympathetic nervous system stress
 Alanine aminotransferase (ALT): a marker of liver injury
Longvida curcumin Increased
 Catalase activity: an antioxidant enzyme
 Antioxidant status: linked to lower levels of damaging free radicals
DiSilvestro RA, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012 Sep
26;11:79. doi: 10.1186/1475-2891-11-79.
In a 30 day, randomised placebo-controlled trial, daily supplementation with 400mg Longvida
curcumin in healthy, middle-aged individuals (40-60 years) led to significant (p<0.05) improvements
(versus placebo) in the following markers:

30. Longvida crosses the blood-brain barrier
• Longvida has been demonsrtated to deliver free curcumin across the blood-brain barrier and is
able to significantly improve markers of cognitive health and brain ageing, including improved
β-amyloid clearance
• Thus low dose Longvida provides the blood concentrations of free curcumin required to
disaggregate β-amyloid plaques and further prevent new plaques from forming
• Longvida is one of the only curcumin dosage forms to show stability of free curcumin in the
bloodstream, meaning extended release with just a single small daily dose
DiSilvestro RA, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012 Sep 26;11:79.
doi: 10.1186/1475-2891-11-79.
Ma QL, Zuo X, Yang F, Ubeda OJ, Gant DJ, Alaverdyan M, Teng E, Hu S, Chen PP, Maiti P, Teter B, Cole GM, Frautschy SA. Curcumin suppresses soluble tau dimers and
corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice. J Biol Chem. 2013 Feb 8;288(6):4056-65.
• The blood–brain barrier is a highly selective semi-permeable membrane barrier that
separates the circulating blood from the brain extracellular fluid in the central nervous
system

31. Curcumin mechanisms (in vivo)
Metals can promote amyloid-β aggregation, and the drug clioquinol, a metal chelator of copper,
zinc and iron, has been shown to dramatically reduce amyloid-β deposits
 Curcumin’s chelation of both iron and copper (but not zinc) has been proposed as one
mechanism potentially contributing to amyloid-β reduction in animal models
Soluble amyloid-β oligomers are more diffusible than amyloid fibrils, highly toxic and increasingly
viewed as playing an important role in AD pathogenesis
Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM.
Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005 Feb 18;280(7):5892-901.
Ono K, Hasegawa K, Naiki H, Yamada M. Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J Neurosci Res. 2004 Mar 15;75(6):742-
50.
 Curcumin can bind to plaques and block amyloid-β
aggregation as well as fibril and oligomer
formation
 Curcumin can inhibit aggregation or promote
disaggregation of amyloid plaques even at low
concentrations
 Curcumin treatment reduces central nervous
system inducible nitric-oxide synthase,
inflammatory cytokines and lipid peroxidation
Curcumin fluoresces (left) during binding to amyloid-β,
versus control (no curcumin) on the right. (Ono 2004)
Curcumin is an established binding agent of amyloid-
β.

32. Longvida curcumin has been shown
in animal models to reduce soluble
tau and elevate heat shock proteins
involved in tau clearance
Ma QL, Zuo X, Yang F, Ubeda OJ, Gant DJ, Alaverdyan M, Teng E, Hu S, Chen PP, Maiti P, Teter B, Cole GM, Frautschy SA. Curcumin suppresses soluble tau
dimers and corrects molecular chaperone, synaptic, and behavioural deficits in aged human tau transgenic mice. J Biol Chem. 2013 Feb 8;288(6):4056-65.
Longvida curcumin offers benefits in Alzheimer's disease
Curcumin reduces tau by directly reducing the activation of tau kinase such as JNK and
GSK3β in neurons and by reducing glial produced inflammatory cytokines that activate
neuronal tau kinases
Curcumin not only directly binds to and limits aggregation of the amyloid β-sheets but
also restores homeostasis of the inflammatory system, boosts the heat shock system to
enhance clearance of toxic aggregates, scavenges free radicals, chelates metals and
induces anti-oxidant response elements!

33. The effect of Longvida curcumin on mood
Cox KH, Pipingas A, Scholey AB. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older
population. J Psychopharmacol. 2015 May;29(5):642-51.
Results
One hour after administration curcumin significantly improved performance on
sustained attention and working memory tasks, compared with placebo
Working memory and mood (general fatigue and change in state calmness,
contentedness and fatigue induced by psychological stress) were significantly better
following chronic treatment
A significant acute-on-chronic treatment effect on alertness and contentedness was
also observed
Longvida curcumin was associated with significantly reduced total and low-density
(LDL) cholesterol levels
Curcumin possesses many properties which may prevent or ameliorate pathological processes underlying age-
related cognitive decline, dementia or mood disorders
Randomised, double-blind, placebo-controlled trial examined the effects of 400mg Longvida curcumin
on
cognitive function, mood and blood biomarkers in 60 healthy adults aged 60-85
Samples taken:
1 and 3 h after a single dose (acute dose)
4 weeks of daily intake (chronic dose)
1 and 3 h after single dose following chronic dose treatment (acute-on-chronic)

34. Longvi da posi t i oni ng

35. Product
features
 Delivers free curcumin
 Crosses the blood-brain barrier
 285x greater bioavailability
 65x higher peak plasma levels
 7x longer lasting action
 Clinically validated to support cognitive &
general health
 Effective at low doses (1 x 500 mg per day)
 Fast onset
 Highly soluble
 Proven stability

36. Serving size: 1 capsule Per serving % RI*
Longvida®
optimised curcumin extract
from turmeric root
(min. 20% curcuminoids)
500 mg n/a
DIRECTIONS FOR USE
Adults: take 1 capsule daily with food. For intensive support,
take 2 capsules daily as a split dose. Do not exceed the dose
unless advised by a healthcare practitioner.
NUTRITIONAL INFORMATION
INGREDIENTS:
Longvida® optimised curcumin extract; capsule shell (emulsifier:
hydroxypropyl methylcellulose); stearic acid; soy lecithin;
maltodextrin; ascorbyl palmitate; silicon dioxide.
Free from: dairy, gluten, lactose, soya protein, wheat, yeast,
artificial colours and flavours; not tested on animals; non-GMO;
suitable for vegetarians & vegans; halal & kosher.
* % Reference Intake
Product information
Permeability  SolubilityStability

37. Curcumin offers synergistic benefits with omega-3 fatty acids
Thota RN et al., Curcumin and long-chain Omega-3 polyunsaturated fatty acids for Prevention of type 2 Diabetes (COP-D): study protocol for a randomised controlled trial. Trials. 2016 Nov 29;17(1):565.
Lerdchai K, et al., Thai Silk Fibroin/Gelatin Sponges for the Dual Controlled Release of Curcumin and Docosahexaenoic Acid for Anticancer Treatment. J Pharm Sci. 2016 Jan;105(1):221-30.
Mirza KA et al., In vitro assessment of the combined effect of eicosapentaenoic acid, green tea extract and curcumin C3 on protein loss in C2C12 myotubes. In Vitro Cell Dev Biol Anim. 2016
Sep;52(8):838-45
Odenthal J et al., The influence of curcumin, quercetin, and eicosapentaenoic acid on the expression of phase II detoxification enzymes in the intestinal cell lines HT-29, Caco-2, HuTu 80, and LT97. Nutr
Cancer. 2012 Aug;64(6):856-63.
Saw CL, et al., Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid. Biochem Pharmacol. 2010
Feb 1;79(3):421-30.
Fiala M. Curcumin and omega-3 fatty acids enhance NK cell induced apoptosis of pancreatic cancer cells but curcumin inhibits interferon-γ production: benefits of omega-3 with curcumin against cancer.
Molecules. 2015 Feb 12;20(2):3020-6.
Halder RCet al., Curcuminoids and ω-3 fatty acids with anti-oxidants potentiate cytotoxicity of natural killer cells against pancreatic ductal adenocarcinoma cells and inhibit interferon γ production. Front
Physiol. 2015 May 22;6:129.
 Ideal to be used alongside Pharmepa RESTORE & Maintain
 Potent synergistic antioxidant and anti-inflammatory health
benefits
 Improved insulin signalling – benefits for type II diabetes
 Improved cognitive functions – benefits for neurocognitive
disorders
Increasing number of studies are showing synergistic health benefits combining
omega-3 EPA & DHA with curcumin

38. Education Technical
Sophie Tully
Nutrition Education Manager
sophiet@igennus.com
Dr Nina Bailey
Head of Nutrition
ninab@igennus.com
Twitter @DrNinaBailey

40. Jäger R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM.
Comparative absorption of curcumin formulations. Nutr J. 2014 Jan
24;13:11.
Directly compare Meriva, BCM95, Curcuwin against curcumin was in a
randomized, double-blind, crossover human study in healthy volunteers
Inclusion of turmeric volatile oils
BCM-95®
Nanoformulations (liposomes, micelles, etc)
Curcuwin (similar to Lonvida)
Curcumin phospholipid complex
Meriva-SR®

41. Jäger R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM. Comparative absorption of curcumin formulations. Nutr J. 2014 Jan 24;13:11. doi: 10.1186/1475-2891-13-
11.
Cuomo J, Appendino G, Dern AS, Schneider E, McKinnon TP, Brown MJ, Togni S, Dixon BM. Comparative absorption of a standardized curcuminoid mixture and its lecithin
formulation. J Nat Prod. 2011 Apr 25;74(4):664-9. doi: 10.1021/np1007262. Epub 2011 Mar 17.
Methods
The relative absorption of a curcumin phytosome formulation (CP - Meriva), a formulation with volatile
oils of turmeric rhizome (CTR - BCM95) and a formulation of curcumin with a combination of hydrophilic
carrier, cellulosic derivatives and natural antioxidants (CHC - Curcuwin) in comparison to a
standardized curcumin mixture (CS - curcumin) was investigated in a randomized, double-blind,
crossover human study in healthy volunteer
Subjects consumed optically identical 6 hard gel capsules of each of the study materials per setting
yielding 376 mg of total curcuminoids for Meriva, BCM95 & Curcuwin and 1,800 mg of total
curcuminoids for standard curcumin. The dose was selected based on Cuomo et al.
Results
Total curcuminoids appearance in the blood was 1.3-fold higher for BCM95 and 7.9-fold higher for
Meriva in comparison to unformulated curcumin. CHC showed a 45.9-fold higher absorption over
curcumin and significantly improved absorption over Meriva (5.8-fold) and BCM95 (34.9-fold, all p<
0.001)
Conclusion
A formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives and natural
antioxidants significantly increases curcuminoid appearance in the blood in comparison to unformulated
standard curcumin Meriva and BCM95
Comparative absorption of curcumin formulations

42. Jäger R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM. Comparative absorption of curcumin formulations. Nutr J. 2014 Jan 24;13:11. doi:
10.1186/1475-2891-13-11.
CurcuwinMerivaStandard curcumin (95%)BCM

43. Jäger R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM. Comparative absorption of curcumin formulations. Nutr J. 2014 Jan 24;13:11. doi: 10.1186/1475-2891-13-
11.
Cuomo J, Appendino G, Dern AS, Schneider E, McKinnon TP, Brown MJ, Togni S, Dixon BM. Comparative absorption of a standardized curcuminoid mixture and its lecithin
formulation. J Nat Prod. 2011 Apr 25;74(4):664-9. doi: 10.1021/np1007262. Epub 2011 Mar 17.
Results in simple terms!
BCM95 (376 mg of total curcuminoids) achieved curcumin plasma levels of 0.5ng/mL
Meriva (376 mg of total curcuminoids) achieved curcumin plasma levels of 2.8ng/mL
Curcuwin (376 mg of total curcuminoids) achieved curcumin plasma levels of 27.3ng/mL
Curcumin (1800 mg of total curcuminoids) achieved curcumin plasma levels of 2.3ng/mL
Total curcuminoids(comparison to unformulated curcumin) appearance in the blood was
1.3-fold higher for BCM95
7.9-fold higher for Meriva
45.9-fold higher for Curcuwin
Curcuwin resulted in 5.8-fold higher curcumin levels than Meriva and 34.9-fold higher curcumin levels
than BCM95
Curcuwin seems superior!!
But.....lets look back at the study by Cuomo
Whilst this study gives the appearance that
Curcuwin is superior 376mg raises levels to 27ng/mL
Which is less than the comparable dose reported by
Cuomo which achieved levels of 50.3ng/mL
Comparative absorption of curcumin formulations
Cmax (ng/mL
Jäger
(Meriva)
Cuomo
(Meriva)
Jäger
(Cucuwin)
Curcumin 2.8 50.3 27.3
DMC 5.0 134.6 5.4
BDMC 0.8 24.9 1.4
Total curcumoids 8.6 206.9 34.9