2011 xanthigen presentation april 2011
TRANSCRIPT
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THE EFFECTS OF XANTHIGEN IN THE WEIGHT MANAGEMENT OF OBESE
PREMENOPAUSAL WOMEN WITH NON‐ALCOHOLIC FATTY LIVER DISEASE AND
NORMAL LIVER FAT (DIABETES, OBESITY, AND METABOLISM 12:72‐81,2010).
with Polifenoles Naturales
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• Obesity and overweight pose a major risk for chronic diseases, including
type 2 diabetes, cardiovascular disease, hypertension and stroke, and
certain forms of cancer, i.e. breast (postmenopausal), endometrium (the
lining of the uterus), colon, kidney, and esophagus. Some studies have
also reported links between obesity and cancers of the gallbladder,
ovar es, an pancreas.
• The non‐fatal, but debilitating health problems associated with obesity
include respiratory difficulties, chronic musculoskeletal problems, skin pro ems an n ert ty.
• In the analyses carried out for World Health Report 2002, approximately
58% of diabetes and 21% of ischemic heart disease and 8‐42% of certain
cancers g o a y were a r u a e o a a ove g m .• The key causes are increased consumption of energy‐dense foods high in
saturated fats and sugars, and reduced physical activity.
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The Liver Can Become Fat‐Clogged
Nonalcoholic Fatty
Liver
Disease
(NAFLD)
occurs when fat is not utilized properly
and accumulates inside liver cells. An imbalance in the liver’s ability to regulate
fat roduction distribution and utilization is linked to the radual accumulation
of fat in the body.
Normal Liver (NLF) Fatty Liver (NAFLD)
Less than 5% fat More than 5% fat
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Xanthigen
(Undaria pinnatifida and Laminaria japonica) and
Pomegranate Seed Oil (Punica granatum)
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Historic Food Use
Brown Seawee
Laminaria (Kombu) and Undaria (Wakame) are the most popularly
consumed brown marine vegetables in soup, salad and snacks.
Wakame and Kombu were originally obtained from wild crops ‐‐ today by
large‐scale cultivation methods in Asia.
Pomegranate
Pomegranate seeds are edible and are often consumed along with the
flesh.
As “anardana” they are used as a spice in Indian, Persian, and Pakistani
cuisine, for example in Aloo Anardana (potatoes with pomegranate seed
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TITLE 21‐‐FOOD AND DRUGS
CHAPTER I‐‐FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER E‐‐ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS
• PART 582 ‐‐ SUBSTANCES GENERALLY RECOGNIZED AS SAFE (GRAS)
Subpart A‐‐
General Provisions
Sec. 582.40 Natural extractives (solvent‐free) used in conjunction with spices,
seasonings, and flavorings.
Natural extractives (solvent‐free) used in conjunction with spices, seasonings, and
flavorings that are generally recognized as safe for their intended use, within the
meaning of section 409 of the act, are as follows:
Algae, brown Laminariaspp. andNereocystisspp.
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Clinical Study Design
• Institute of Immuno atholo ‐ Russian Academ of Natural Sciences (Moscow)
• Effect of Xanthigen in obese subjects with NLF and NAFLD, double blind placebo controlled, randomized
• ,
• 3 softgels/day (total 600mg Xanthigen/day) ; 1800 kcal prepared diet
• visits 3 times/week and weekly measurements:
Body weight, body fat and liver fat measured by DEXA, resting
energy expenditure measured by indirect calorimetry, waist
circumference, triglycerides, ALT, AST, GGT, CRP, systolic and
Results published: Abidov M, Ramazanov Z, Seifulla R, Grachev S. The effects of
Xanthigen in the weight management of obese premenopausal women with non-
alcoholic fatty liver disease and normal liver fat. Diabetes Obes Metab. 2010
Jan;12(1):72-81.
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L D )
Placebo1 Xanthigen1 Placebo2 Xanthigen2
e uce ver a con en prece es o y a oss
n ‐ A l c o h
o l i
L i v e r ( N
A
14
16
18
)
A. Significant NAFLD liver
fat loss at 7 weeks
precedes significant body
N
F a t t y
F )6
8
10
i v e
r F a t (
fat loss at 8 weeks.
H e a l t h
L i v e r ( N
0
2
4
B. Signficant NLF liver fat
loss at 5 weeks precedes
significant body fat loss at 6
weeks.
Time (weeks)
↑ = statistically significant liver fat loss
Diabetes, Obesity,
and
Metabolism
12:72‐81,2010.
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Placebo Xanthigen
Effect of Xanthigen on body weight in obese subjects with NLF
94
96
98
)
88
90
92
W e i g h t ( k g s
82
84
86
B o d y First time point showing
statistically significant
weight loss
80
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Time (weeks)
Diabetes, Obesity,
and
Metabolism
12:72‐81,2010.
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Placebo Xanthigen
Effect of Xanthigen on body weight in subjects with NAFLD
94
96
)
88
90
92
e i
g h t ( k g
84
86
B o d y
First time point showing
statistically significant
weight loss
80
82
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Diabetes, Obesity,
and
Metabolism
12:72‐81,2010.
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Xanthigen vs. Fucoxanthin or Pomegranate Seed Oil
1400
1600
1800
d ) N e t
e **
* p<0.05
800
1000
1200
1670 1686
t o t a l E E / k J
v e r b a s e l i n
*
*±310
±290
200
400
58
591
230
778
1152
159 173
R E E (
±210
±147
±260
±290
±65 ±92±40
±40
Diabetes, Obesity,
and
Metabolism
12:72‐81,2010.
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Xanthigen Improves Liver Health Markers
A group of 72 volunteers with fatty liver disease had elevated liver serum
enzymes (ALT, AST and GGT) and C‐reactive protein (a marker of chronic inflammation), which Xanthigen actually improved.
Preclinical and postclinical characteristics of obese non‐diabetic female volunteers with NAFLD and
NLF.
NAFLD NLF
Measurement Pre Placebo Pre XanthPost Placebo Post Xanth Pre Placebo Pre Xanth
Post Placebo Post Xanth
TG, mg/dl 191 ± 15 195 ± 19 180 ± 17 158 ± 21† 174 ± 12 177 ± 12 168 ± 11 155 ± 14§
ALT, U/l 51 ± 9 48 ± 7 40 ± 6 26 ± 7† 31 ± 9‡ 33 ± 7‡ 28 ± 6 26 ± 7§
AST, U/l 53 ± 7 51 ± 5 46 ± 6 29 ± 6† 33 ± 7‡ 38 ± 5‡ 29 ± 6 29 ± 2§
GGT, U/l
49
± 5
47
± 7
46
± 6
31
± 5†
29
± 3‡
27
± 3‡
26
± 2
21
± 3§
CRP, mg/l 6.3 ± 2.1 6.2 ± 2.4 5.4 ± 2.1 3.6 2.2† 5.4 ± 2.4 5.4 ± 2.6 5.1 ± 2.1 3.9 1.8†
†p < 0.05 compared to placebo.
‡p < 0.05 compared to the baseline values in the other cluster.
§ p = NS compared to placebo.
Diabetes, Obesity,
and
Metabolism
12:72‐81,2010.
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Summary of Results
• Xanthi en was well tolerated with no safet concerns.
• Xanthigen is effective in reducing body weight and liver fat at a dose of 600mg/day (200mg tid).
• ant gen at t e propose ose n uce a net ncrease o y
KJ/24h which was statistically significant when compared with baseline REE and
with placebo.
• ere was a s a s ca y s gn can re uc on n o y we g a er wee s
and 8 weeks (NAFLD). Participants lost an average of 5.5 kg (NAFLD) and 4.9 kg
(NFL) MORE THAN the placebo groups by the end of the study.
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Summary of Results
• The bod wei ht reduction was receded a roximatel 1 week rior b a
significant reduction in the liver fat content on week 5 (NFL) and week 7 (NAFLD).
• The weight reduction correlated with body fat loss and waist circumference
reduction.
• Laboratory parameters (liver enzymes and triglyceride levels) and blood pressure
were also significantly improved compared to baseline.
• an gen seems o possess o er a c v y ene c a o e overa p c ure o
obesity and the related metabolic syndrome
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Xanthigen
600mg/day
Proposed Xanthigen Mechanism
Overweight/
ObeseNFL
UCP1 upregulation
Liver Fat
Decrease
Increased Resting
Energy Expenditure
(REE)
Body Weight
Decrease
Improved Levels
of Inflammation
MarkersImproved Blood
Lipids & Liver
Enzymes
Improved
Cardiovascular
Health & Blood
Pressure
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Obesity and Liver Health: A unique approach
“The liver
acts
as
a filter
in
the
body
and
once
it
is
‘clogged’
with
fat
it
cannot function properly, a condition clearly linked with fat accumulation
in other tissues and obesity.”
‐‐
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Xanthigen ® the “Youth Factor”
Effects of Fucoxanthin, Xanthigen and pomegranate seed oil on SIRT‐1 protein
expression in 3T3‐L1 adipocytes
Fucoxanthin and Xanthigen markedly increased SIRT-1 protein levels in differentiated 3T3-L1 adipocytes,
whereas cells treated with pomegranate seed oil did not show change in SIRT-1 expression as compared to the
untreated, control cells.
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Xanthigen ® the “Youth Factor” Future Experimental Directions
Does Xanthigen biological effects share mechanisms of lifespan extension similar to that
afforded with calorie restriction diet? Does Xanthigen has an advantage over the calorie
restriction diet?
1. Insulin production
ancreatic
-cells6. Adiponectin
Table1. The effects of Calorie restrict ion (CR)
on markers of aging
1. Insulin production
ancreatic
-cells6. Adiponectin
Table1. The effects of Calorie restrict ion (CR)
on markers of aging
1. Insulin production
ancreatic
-cells6. Adiponectin
Table1. The effects of Calorie restrict ion (CR)
on markers of aging
2. Fat storage
( white adipose tissue)
3.Insulin sensitivity
7. AMPK activation
( pancreatic -cells)
8. mTOR activation
2. Fat storage
( white adipose tissue)
3.Insulin sensitivity
7. AMPK activation
( pancreatic -cells)
8. mTOR activation
2. Fat storage
( white adipose tissue)
3.Insulin sensitivity
7. AMPK activation
( pancreatic -cells)
8. mTOR activation
(liver and muscles)
4.Glucose and insulin levels
(blood )
5.Glucose uptake
9. Fatty acid oxidation
10. SIRT1
(most tissue)
11. IGF
(liver and muscles)
4.Glucose and insulin levels
(blood )
5.Glucose uptake
9. Fatty acid oxidation
10. SIRT1
(most tissue)
11. IGF
(liver and muscles)
4.Glucose and insulin levels
(blood )
5.Glucose uptake
9. Fatty acid oxidation
10. SIRT1
(most tissue)
11. IGF( skeletal muscle and fat pads)
12. ROS
13. Inflammation
(IL-6, TNF-
, NFκ
-B)
( skeletal muscle and fat pads)
12. ROS
13. Inflammation
(IL-6, TNF-
, NFκ
-B)
( skeletal muscle and fat pads)
12. ROS
13. Inflammation
(IL-6, TNF-
, NFκ
-B)
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