November 18, 2016

CONFIDENTIAL

REPORT: COMPARISON OF HUMAN ABSORPTION

STUDIES ON ACUMIN AND CURCUWIN AND OTHER
CURCUMIN INGREDIENTS
Luke R. Bucci, PhD CCN CNS
Scientific Advisory Board Member, Novel Ingredients
& InnerPath Nutrition

Purpose:
This review of human absorption (bioavailability) studies on curcumin materials used in dietary
supplement products explores the comparative absorption reported in promotional literature
taken from the actual studies.

Background:
Both Acumin and CurcuWIN have reported on absorption into blood of curcumin compared to
standard curcumin powder (95% curcumin or curcuminoids), an oleoresin preparation (Dolcas
Biotech’s BCM95) and a phospholipid preparation (Indena’s Meriva). Comparison of studies is
complex and difficult due to the nature of curcumin metabolism in the human body, differing
doses, differing forms of curcumin measured, differing effects on bioavailability of ingredient
preparations, different treatments of blood before analysis, and inadequate reporting of
experimental details. This comparison will point out what the real-life messages are for each
ingredient.

Absorption Claims:

Acumin
What is it? A reconstructed turmeric root preparation standardized to 45-50% curcuminoids
(curcumin, demethoxycurcumin & bisdemethoxycurcumin) – same ratios as turmeric root.
Turmeric root is extracted with food-grade ethanol to purify curcuminoids. The extracted mass is
treated with water for a standardized mixture of carbohydrates, fibers and turmerin protein (40,
5, 2 % respectively). Turmeric root essential oil is prepared. All three preparations are blended
by a patent-pending process to make a Polar/Nonpolar Sandwich (PNS) material, essentially
coating curcuminoids as in turmeric root but with high and commercially feasible standardized
curcumin amount (~50%). Thus, curcumin in Acumin is as close to food use of turmeric as
possible, and completely different from all other enhanced-absorption curcumin materials.

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CurcuWIN
What is it? CurcuWIN is a patented composition (US9259401) of purified curcumin,
antioxidants (mixed tocopherols & ascorbyl palmitate), fat and hydrophilic carriers. Fat is chosen
from hydrogenated vegetable oils, MCTs, milk fat, long chain triglycerides. Carriers are one or
more of soluble starch, modified celluloses, polyvinyl pyrrolidone (PVP), polyethylene glycols
(PEGs), glycerol, sorbitol, mannitol, glucose and sucrose. OmniActive website declares
hydroxypropylmethylcellulose, PVP and unspecified starch as components of CurcuWIN. Thus,
the exact composition of CurcuWIN is not known, and additional excipients may be present.
Curcumin content is 20% cucuminoids in same ratio as turmeric root.

Acumin Absorption Data – Comparison to Standard 95% Dry Curcumin

There are two human absorption studies on Acumin (formerly named CureIt in one article) (Gopi
et al, AsianJPharmTechInno 2015; Gopi et al, submitted for publication, 2016). In a crossover
study, 12 subjects were given 500 mg 95% curcuminoids and 500 mg Acumin (~250 mg
curcuminoids). Blood plasma was collected and extracted with ethyl acetate (EtAc), and total
curcumin measured from 0-12 hours. This extraction method is a measure of free and conjugated
(total) curcumin levels, although data on solubility of curcumin glucuronides in EtAc are not
found, and may be an underestimate of actual curcumin absorbed. Cmax (ng/ml) was 43.1 and
434 for curcuminoids and Acumin, with large standard deviations (typical of between-subjects
variations in quantitative measurements of curcumin absorption in humans). Thus, Gopi et al
reported a 10fold increase in curcumin absorption for Acumin compared to standard dry powder
curcuminoids. Correcting for difference in dose, Acumin was 20 and 10.8-fold higher than dry
curcuminoids for Cmax and AUC 0-8 hours, respectively (See Table).

CurcuWIN Absorption Data – Comparison to Standard 95% Dry Curcumin

Jager et al, NutrJ 2014 reported on comparative absorption of CurcuWIN with standard dry 95%
curcuminoids, and reported a 45.9-fold increase from CurcuWIN in the article (shown as 46-fold
on OmniActive’s website page for CurcuWIN). This study was also a crossover design with 12
subjects measured from 0-12 hours for Total Curcuminoids. The analysis of curcumin was
completely different from the Acumin study. Plasma was collected and treated with an enzyme
mixture to convert glucuronidated, sulfated and methylated conjugates to free curcumin, since
the authors noted that free curcumin was not present or extremely low in plasma in previous
studies on curcumin absorption. Therefore, CurcuWIN measured Total Curcuminoids, including
tetrahydrocurcumin and its metabolites (a small quantitative difference), and did not measure
free curcumin. In addition, the data was natural-log-transformed for statistical analysis (curve-
fitting) and then reported as antilog (i.e., untransformed) which is a statistical method to reduce
between-subject variability. This statistical practice gives smaller error bars but does not reflect
the real-life individual variations reported by others, including the Gopi 2015 Acumin study. The
curcuminoids doses tested were 1800 mg curcuminoids and 376 mg curcuminoids from
CurcuWIN.
The Total Curcuminoids were increased from a Cmax of 5.2 ng/ml for dry curcuminoids
to 34.9 ng/ml for CurcuWIN. The Relative Absorption was reported in Table and Graphical

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forms. This relative increase by CurucuWIN over dry curcuminoids, corrected for the difference
in dose is 32.1-fold for Cmax, and 45.9-fold for AUC 0-12 hours (reported on website and
promotional materials).
Although the relative difference between CurcuWIN and Dry standard appears to be large
(46x), this difference is deceiving. The quantitative improvement by CurcuWIN was modest
compared to Acumin. Thus, the relative improvement is compared to a very low value for which
even a modest improvement will look larger than it actually is directly. An analogy is being 46
times bigger than a mouse two-cell embryo, whereas Acumin is “only” 10 times bigger than an
adult mouse. Obviously it is quantitatively better to be 10x bigger than an adult mouse than 46x
bigger than a few mouse cells.
Oddly, the plasma levels of Total Curcuminoids for CurcuWIN, curcuminoids and other
products never reached baseline and some did not decrease from the peak at one hour. This result
(lack of dropoff of plasma curcumin levels by 12 hours) is aberrant from all other curcumin pK
human studies and does not match prior published data from the other curcumin products tested.
This finding raises questions about the analysis and calculation of results.

Comparison of Acumin and CurcuWIN Absorption Data

Table: Acumin and CurcuWIN Human Absorption Data

Material Tested Curcumin Dose Cmax AUC 0-12 hour Relative
(mg) (ng/ml) (ng/ml-hr) Absorption
Dry Curcumin 500 43.1 166 ---
(Acumin Study)
Acumin 250 434 904 20 / 10.8*
Dry Curcumin 1800 5.2 40 ---
(CurcuWIN Study)
CurcuWIN 376 34.9 380 32 / 46*
Acumin/CurcuWIN 0.66 12.4x 2.4x 19 / 3.6*
Dry Curcumin 0.28 1.23x 4.15x 4.4 / 15*
Acumin / Dry
Curcumin
CurcuWIN
*corrected for dose

As can be seen in the comparison of human absorption data between Acumin and CurcuWIN
studies, there are large differences that are not apparent from promotional literatures. First, the
absorption of standard dry 95% curcuminoids used in both studies does not match. Curcumin
was absorbed more in the Acumin study, exhibiting a similar peak and cumulative plasma level
from a dose 3.6-fold less. This may indicate a ceiling effect of higher dry curcumin doses not
achieving higher plasma levels at these dose ranges. Or it may indicate that methodological
differences and statistical transformations may exaggerate differences in plasma levels.

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Although not the topic of this report, the other relative comparisons between CurcuWIN and
other curcumin materials is similarly fraught with inappropriate comparisons based on what each
study measured and those quantitative results. Also, a single dose-response study does not affect
other successful human intervention trials – it merely indicates inappropriate or irrelevant
comparisons are misleading and not useful.

Likewise, direct comparison of ng/ml total curcumin plasma levels between Acumin and
CurcuWIN showed superiority of Acumin by both Cmax and AUC values without dose
correction and even larger after dose normalization (Relative Absorption), as per how CurcuWIN
compared itself to dry curcumin.

Differences Between Acumin and CurcuWIN Materials

Acumin CurcuWIN
45-50% Curcumin 20% Curcumin
Curcuminoid spectrum equal to root Curcuminoid spectrum equal to root
Food-grade ethanol extraction for Starts with purified curcumin from unknown
curcuminoids concentration, otherwise water extraction method
extraction
Contains turmeric root components (turmerin, Only pure curcumin, no other turmeric root
turmerones, fiber, lipids, carbohydrates components
standardized – there are at least 200 known
compounds in turmeric root)
Carbohydrate/Fiber/Protein/Lipid Nonpolar Mixture of curcumin with fat and emulsifying
sandwich technology agents, some of which may not be described
Patents pending for composition Patent granted for composition
Closely approximates turmeric root No turmeric components remain
composition (food-like) (pharmaceutical-like)
Superior relative absorption to dry 95% Superior relative absorption to dry 95%
curcuminoids curcuminoids
Superior relative absorption to CurcuWIN Inferior relative absorption to Acumin
100% “Natural” (food extract) Unknown percentage of synthetic excipients

Summary
Human studies of curcumin ingredients absorption are complex and often opaque for
experimental details. So far, few curcumin ingredients have measured free curcumin in plasma or
non-plasma tissues/compartments. Thus, knowledge of actual metabolic fates of ingested
curcumin is poorly known for any material. There is tantalizing evidence that free curcumin is
powerful from in vitro and some animal experimentation. But free curcumin has not been found
at effective doses that match in vitro concentrations in humans. It is likely that most studies have
been looking the wrong way in the wrong places. Given results of efficacy from a variety of
human intervention studies using dry curcumin and enhanced absorption forms, it is apparent

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that absorption (bioavailability, pK) studies in humans are not conclusive for any determinations
other than little or no free curcumin is found in plasma.

Thus, results and comparisons of human absorption data from curcumin and enhanced absorption
curcumin materials must be viewed with caution and not taken as completely credible. What is
credible is the large body of evidence from long-term human ingestion of curry containing
turmeric being associated with improvements in health of cardiovascular, mental,
musculoskeletal and immune systems. Thus, a proper strategy to reproduce curcumin benefits
from epidemiological and observational studies would be to mimic the composition of turmeric
as closely as possible with higher intakes in short durations to mimic long-term use. At this
point, Acumin represents the closest match to turmeric and exhibits clinically documented
uptake into plasma consistent with other curcumin forms that also show enhanced uptake into
plasma.

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