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Dietary Supplement Information for Physicians
with Naturokinetics®
GI Guard™ PM
Product Code P2997
Category: GI Tract Support
TECHNICAL SUMMARY
GI Guard™ PM is a specialized, clinically supported combination of dietary zinc and
melatonin formulated to be taken 30 to 60 minutes before bedtime for targeted GI
tract epithelium repair. Zinc in GI Guard™ PM is in the form of Zinc-L-Carnosine
(PepZin GI®), which is a stable complex of Zinc and L-Carnosine, a di-peptide formed
by the amino acids β-alanine and L-histidine. Vitamins B, C and selected amino acids
are included for additional restorative effect.
Common Name:
Chemical Name:
Zinc-L-Carnosine, Polaprezinc
Zinc N-(3aminopropionyl)histidine
Melatonin
N-Acetyl-5methoxytryptamine
C9H12N4O3Zn
C13H16N2O2
289.63 g/mol
232.28 g/mol
Chemical
Structure:
Molecular
Formula:
Molecular Weight:
Product Composition: Folic Acid, L-Tryptophan, L-Methionine, Betaine, Taurine,
Zinc-L-Carnosine, Cyanocobalamin, Pyridoxine HCl, Ascorbyl Palmitate, Melatonin,
Cellulose, Stearic Acid (vegetable source), Croscarmellose Sodium and Silica.
Vegetarian/vegan.
Delivery Form: Tablets.
ROLE AS A NUTRIENT
Essentiality and Dietary Sources:
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 Zinc is an essential mineral. Recommended daily intake for zinc is 15 mg/day. Zinc is found in a variety of plant foods.
Carnosine, which is present in large quantities in muscle tissue, is a di-peptide composed of β-alanine (non-essential
2
amino acid) and L-histidine (essential amino acid). Carnosine is abundant in meat products and eggs.
3
 Melatonin is synthesized in the body from L-tryptophan and is ubiquitously present in all animals.
Methods of Evaluating Nutritional Status:
 In adults, normal plasma zinc level is 60-130 µg/dL.
4
 Melatonin can be detected in plasma or saliva; its concentration strongly correlates with the circadian rhythm.
Structural and Functional Role:
 Zinc is known for its stabilizing and anti-inflammatory effect on gastric mucosa. This effect is enhanced by slow
dissociation of Zinc-L-Carnosine which causes zinc to stay within the GI tract long enough to bind to the injured
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epithelium, while L-Carnosine simultaneously helps to neutralize free-radicals in and around the damaged mucosa.
 Melatonin was initially considered to be a systemic hormone exclusively derived from the pineal gland. It influences a
variety of biological processes including neuroendocrine, immune and cardiovascular functions, as well as circadian
rhythms. Melatonin has also been shown to be generated locally by neuroendocrine cells in many tissues, including
those of the GI tract. In the gastric mucosa, melatonin acts via specific membrane receptors and also as a free-radical
scavenger. It exerts a protective, anti-inflammatory effect on the gastric lining, helps support healthy pH levels, and
6
supports normal pepsin and gastrin production. Additionally, taken at bedtime, melatonin reduces difficulties
7
associated with falling asleep and improves symptoms associated with poorly coupled circadian rhythms.
PepZin GI® is a registered trademark of Hamari Chemicals, Ltd.
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Dietary Supplement Information for Physicians
with Naturokinetics®
RECOMMENDED USE
NATUROKINETICS®
Liberation: Dissolution data is not available. GI Guard™ PM P2997
tablets pass the standard disintegration test (< 60 minutes).
Absorption:
 Due to slow dissociation, absorption of zinc from Zinc-L-Carnosine
is significantly delayed, which allows for adhesion of zinc ions to
gastric epithelium. Elevated gastric Zn concentration is maintained
for a significantly longer period of time after Zinc-L-Carnosine
compared to zinc sulfate administration (Figure 1). Peak plasma Zn
10
concentration is reached in ~ 4 hours (Tmax). The amount of Zn
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absorbed from Zinc-L-Carnosine is estimated to be 11%.
 In healthy volunteers with normal sleep-awake cycle, single
administration of 2 or 4 mg melatonin tablets results in maximum
plasma concentrations in ~ 1 hour (Tmax) with absolute
bioavailability of about 15% due to significant first-pass hepatic
12
metabolism (Figure 2).
Distribution:
 Absorbed zinc and L-carnosine are distributed to the liver, kidney,
prostate; and to a lesser extent to the testes and brain where zinc
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uptake is tightly regulated by the blood-brain barrier.
 Melatonin is subject to systemic distribution and easily crosses the
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blood-brain barrier.
Metabolism:
 Metabolism of exogenous L-carnosine is similar to that of
endogenous carnosine, which is hydrolyzed to β-alanine and L13
histidine by carnosinase in the blood, liver, and kidneys.
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 Melatonin is metabolized in the liver into 6-sulfatoxymelatonin.
PepZin GI® is a registered trademark of Hamari Chemicals, Ltd.
Radioactivity (µmol • eq/content)
Support of Normal Gut Permeability: In a double-blind, placebo-controlled, crossover clinical trial with ten healthy
volunteers (24–40 years old), five days of consecutive indomethacin administration (50 mg three times a day, days 3-7) plus
placebo (days 1-7) caused a threefold increase in gut permeability (assessed as lactulose/rhamnose ratio) whereas no
significant increase in permeability was detected when indomethacin was co-administered with Zinc-L-Carnosine (37.5
5
mg/twice a day, days 1-7).
Support of Gastric Mucosa: In a randomized, placebo-controlled, clinical trial with 20 adult volunteers, supplementation
with melatonin in the dose of 5 mg 30 minutes prior to administration of aspirin (1 gram twice a day for 11 days) resulted in
significant protection of gastric mucosa as compared to aspirin plus placebo. The evaluation was conducted endoscopically
using standardized Lonza score, which demonstrated 90% attenuation of lesions and 50% reduction in microbleeding when
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melatonin was co-administered.
Support of Esophageal Mucosa: In a prospective clinical trial with 36 volunteers with Gastro-Esophageal Reflux Disease
(GERD) and healthy individuals as control, baseline plasma melatonin level was found to be significantly lower (~ 50%) in
patients with GERD. Supplementation with melatonin (3 mg at bedtime) resulted in significant improvement in heartburn
and epigastric pain symptoms, lowered esophageal sphincter pressure, and raised serum gastrin and melatonin levels
following 4 and 8 weeks of therapy. The outcomes were comparable
8
with omeprazole treatment.
100
Support of Intestinal Mucosa: In a randomized, double-blind, placebo
controlled clinical trial with 40 female IBS patients with sleep
*
10
disturbances, supplementation with melatonin (3 mg at bed time for 2
weeks) significantly decreased mean abdominal pain score (p < 0.001)
1
9
as compared to placebo.
0.1
0.01
0.001
0
2
4
6
8
Time (hr)
Figure 1: Time course of total mean radioactivity in
gastric contents after oral administration of Zinc in the
form of polapresinc or zinc sulfate (  65Zn polaprezinc;
 65ZnSO4; *P < 0.05).
Figure 2: Mean serum concentration versus time
profile following single oral administration of 2 and
4 mg of melatonin tablets in healthy volunteers.
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Dietary Supplement Information for Physicians
with Naturokinetics®
Elimination:
65
 Following a single administration of radiolabeled Zinc-L-Carnosine, 85% of Zn was eliminated with feces and 0.3%
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with urine.
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 Predominant route of elimination of melatonin and its metabolite 6-sulfatoxymelatonin is via urine.
SAFETY INFORMATION
Tolerability:
 Upper limit for zinc is 40 mg/day. In clinical trials with typical daily dose of 75 mg, Zinc-L-Carnitine (containing 16 mg
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elemental zinc) was well tolerated for up to 12 weeks, with a negligible amount of gastrointestinal complaints.
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 Doses of melatonin as high as 50 mg/kg of body weight have been used in humans without reported adverse effects.
Cautions: Do not drive or use machinery for 4 to 5 hours after taking melatonin.
INTERACTIONS
Drug Interactions:
 Zinc has been shown to decrease the absorption of cisplatin, penicillamine, quinolone, and tetracycline antibiotics due
to forming insoluble complexes with these medications in the gastrointestinal tract and thus reducing their systemic
availability. Patients should be advised to take these drugs at least 2 hours before or 4-6 hours after zinc
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supplements.
 Concomitant use of melatonin with alcohol, benzodiazepines, or other similar drugs might cause increased sedation.
Melatonin may exhibit interaction with anti-coagulant/anti-platelet medications, antidepressants, anti-hypertensive,
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and anti-diabetes drugs.
Supplement Interactions:
 Zinc may inhibit function of supplemental enzymes, including bromelain. Large amounts of supplemental zinc can
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competitively inhibit copper, magnesium and iron absorption. Zinc may increase manganese absorption when taken
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together.
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 Melatonin may potentiate effect of the supplements with sedative component (5-HTP, kava, valerian root).
Interactions with Lab Tests:
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 Supplementation with elemental zinc 50 mg/day has been shown to raise HgbA1C in type I diabetics.
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 Melatonin supplementation can increase human growth hormone serum levels and decrease serum luteinizing
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hormone levels.
Stability & Storage: Effective through the expiration date when stored in a cool, dry place.
References:
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genotype, are associated with reduced muscle carnosine levels in humans. Amino Acids. Apr 2011; 40 (4): 12211229.
Mercolini L, Mandrioli R, Raggi MA. Content of melatonin and other antioxidants in grape-related foodstuffs:
measurement using a MEPS-HPLC-F method. J Pineal Res. Aug 2012; 53 (1): 21-28.
Benloucif S, Burgess HJ, Klerman EB, et al. Measuring melatonin in humans. Journal of clinical sleep medicine :
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Reflux Disease. BMC gastroenterology. 2010; 10: 7.
PepZin GI® is a registered trademark of Hamari Chemicals, Ltd.
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Dietary Supplement Information for Physicians
with Naturokinetics®
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PepZin GI® is a registered trademark of Hamari Chemicals, Ltd.
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