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Zylkene/Lactium (alpha-casozepine)

Posted by Horned One on June 22, 2008, at 17:43:29

I picked up a leaflet on this at the vet's the other day. It's a new anti-anxiety pill for dogs to help the cope with fireworks, moving house, seperation anxiety and other canine stressors. Obviously I wondered what was in it. Turns out it's concentrated peptide found in cow's milk, which binds to the GABA-A receptor and is superior to diazepam in some models of animal anxiety.

I thought of getting a sample from the vet (ostensibly for the dog), but I found a product called Lactium from Finland that contains the same active ingredient and is marketed for humans:

1: Eur J Nutr. 2005 Mar;44(2):128-32. Epub 2004 Nov 2.
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Effects of a tryptic hydrolysate from bovine milk alphaS1-casein on hemodynamic responses in healthy human volunteers facing successive mental and physical stress situations.

Messaoudi M, Lefranc-Millot C, Desor D, Demagny B, Bourdon L.

ETAP-Applied Ethology 13, rue du Bois de la Champelle, 54500, Vandoeuvre-lès-Nancy, France.

BACKGROUND: Preclinical results in rats have demonstrated anxiolytic-like effects of a tryptic bovine alphaS1-casein hydrolysate. AIM OF THE STUDY: We investigated the putative effects of this tryptic hydrolysate on systolic (SBP), diastolic (DBP) blood pressures, heart rate (HR) values and plasma cortisol concentrations (CC) in human healthy volunteers facing successive stress situations. METHODS: The subjects were (double blind) randomly allocated to ingest three times, 12 hours apart, two capsules containing either 200 mg of alphaS1-casein hydrolysate (TS) or bovine skimmed milk powder as a placebo (CS). On the morning of the test day, a first blood sample for baseline measurement of CC was taken before the subjects were submitted to the Stroop test (ST) and, after a 30-min rest, to a Cold Pressor test (CPT). SBP, DBP, and HR were continuously recorded for 5 min before the ST and during each stress situation. A second blood sample was taken 15 min after the end of the CPT condition. RESULTS: ST and ST + CPT combined test situations increased SBP, DBP and HR. The significant "Treatment x SBP" and "Treatment x DBP" interactions indicated the lower percentage changes in SBP and DBP of the TS. In addition, the results showed a significant decrease of the CC in the TS but not in the CS throughout the ST + CPT combined stress tests. HR remained stable in TS between the initial rest period and the CPT unlike what happened in CS. CONCLUSION: On the basis of blood pressure and cortisol changes, these results suggest an antistress profile of this alphaS1-casein hydrolysate in human subjects.

Caseins are a known source of biologically active peptides. In this study,we have shown evidence of a novel anxiolytic activity in a tryptic hydrolysate of bovine alpha (s1)-casein. Injection of 3 mg/kg of this hydrolysate significantly reduced the epileptic symptoms caused by pentylenetetrazole in rats. Anxiety reduction was also observed when the hydrolysate was testedin the elevated plus-maze and in the conditioned defensive burying rat models. Peptides isolated from the hydrolysate were examined for their affinity for the gamma -amino-butyric acid (GABA) type A receptor. Only one peptide, named alpha -casozepine, corresponding to the 91-100 fragment from bovine alpha (s1)-casein, expressed affinity for GABA(A) receptor. In vitro, thepeptide had 10,000 less affinity for the benzodiazepine site of the GABA(A) than did diazepam. However, in the conditioned defensive burying paradigmit was 10-fold more efficient than diazepam. The difference observed between the in vitro and in vivo activity of alpha -casozepine could not been explained by an action via the peripheral-type benzodiazepine receptor; alpha-casozepine had no affinity for this receptor. The alpha -casozepine aminoacid sequence could be related to the carboxyterminal sequence of the polypeptide diazepam binding inhibitor, an endogenous ligand of the central GABA(A) and peripheral-type benzodiazepine receptors.

By Dr. Joseph A. Debé

There are many different ways to cope with stress and anxiety including meditation, medication, massage, exercise, herbs and others. There is an attractiveness in being able to take a pill to reduce stress. The ideal pill would not only be effective, but would be quick acting, free of side effects and not addictive. A new, patented natural product, containing a biologically active peptide, appears to be such a pill.

Food is information, as strange as that may sound. Every time we eat, we are consuming information, which influences a myriad of physiologic processes, culminating in a potentially significant alteration of our overall functioning- including our emotional state. Peptides (chains of amino acids) have been demonstrated to have biologic activity within the body. Think of amino acids as letters of the alphabet. Peptides are words. They convey messages. When consumed as part of a mixed meal, the message conveyed by a given peptide is somewhat muffled by all the other messages in other bioactive food constituents. When isolated and concentrated in supplement form, however, the message comes through loud and clear. Alpha-casozepine is a decapeptide. This means it is a chain of ten amino acids. The message of alpha-casozepine is a powerful whisper: "Relax. Calm down." Alpha-casozepine talks directly to the brain and spinal cord through GABA receptors. These are the same receptors that benzodiazepines act upon. Benzodiazepines are prescription tranquilizers.

In an experiment performed on rats, alpha-casozepine was administered at three different doses and compared against placebo and Diazepam (a benzodiazepine) in tests of anxious behavior. Not only was alpha-casozepine more effective than the placebo but also it was similar in activity to the drug in reducing Global Anxiety Score. Alpha-casozepine acted in a dose dependent manner. In other words, higher doses of alpha-casozepine were more effective at reducing anxiety than were lower doses.

Does alpha-casozepine offer any advantage compared to benzodiazepines? Animal studies have examined the safety of alpha-casozepine and have determined that it does not produce the side effects associated with benzodiazepines. Importantly, unlike benzodiazepines, alpha-casozepine doesn't impair memory, is not addictive, and does not produce tolerance (lose its effect over time).

Alpha-casozepine is found in nature in milk. Observing that warm milk has a calming affect on babies, researchers endeavored to isolate the active component. The first isolate was a milk protein hydrolysate (an enzymatically cleaved protein fraction). It was later discovered that alpha-casozepine was the peptide responsible for the anxiety-reducing affects of this milk protein fraction. Some research has used alpha-casozepine. Other research has used the milk protein hydrolysate (called Prodiet F 200) that contains it.

One animal study compared Prodiet F 200, St. John's Wort, Kava-Kava, Diazepam and saline solution as a control, for their ability to reduce anxiety. Global Anxiety Scores for the rats treated with Diazepam and Prodiet F 200 were significantly lower compared to the saline group. The rats given St. John's Wort and Kava-Kava did no better than the saline group. Prodiet F 200 reduced anxiety but these two popular herbs did not.

There have been two studies performed on humans using Prodiet F 200. Both human studies have found Prodiet F 200 to reduce measures of stress and anxiety.

In one experiment, Prodiet F 200 was studied in 42 men. They were divided into two groups of 21 each. One group received a skim milk placebo. The other group was given Prodiet F 200. The study was double-blind, meaning neither the test subjects nor the experimenters knew who was receiving which treatment. The day before the test, the test subjects took their assigned product with breakfast and with dinner. On the test day, they took it with a standard breakfast then underwent evaluation. Two different standard tests were done to assess the production of a stress response. One test was psychological in nature, the other more physical. The Stroop test is a challenging mental exercise that results in stress and anxiety. The cold pressor test stresses the nervous system by immersing the hand in cold (2° C) water. Stress response to these tests were assessed using measures of heart rate, systolic and diastolic blood pressure, as well as blood levels of the stress hormones ACTH and cortisol. Results of this study revealed that subjects taking Prodiet F 200 experienced less stress in response to both the Stroop test and the cold pressor test. Across the board, Prodiet F 200 was associated with lower heart rate, lower systolic and diastolic blood pressure, as well as lower levels of ACTH and cortisol. This study demonstrated the rapid onset of action of Prodiet F 200.

Prodiet F 200 is a foreign product. In the United States it is sold under the name of De-Stress. For individuals weighing 110 pounds or less, the recommended dose for De-Stress is one capsule before bed and one during the day at time of intense stress. For heavier individuals, the dose is doubled.





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