fatnews.com Home page  >  Article | Previous article | Next article

SEARCH

QUICKLINKS AND VIEW OPITONS

  • Categories of Articles
  • Summary View
  • Headline View
  • Archive of Quotes
  • Contact Us
  • Follow @fatnews

    Alpha lipoic acid causes “profound weight loss” in rodents


    Posted by .(JavaScript must be enabled to view this email address)
    Monday, August 16, 2010 10:18 am Email this article
    The nutritional supplement alpha-lipoic acid "causes profound weight loss in rodents by reducing food intake and enhancing energy expenditure," according to a recent study. Dose-Dependent Weight Loss

    Weight loss was dose-dependent, that is, the higher the dose of alpha lipoic acid, the greater the weight loss.

    The first study lasted two weeks.

    Alpha Lipoic Acid causes dose-dependent weight loss

    Alpha lipoic acid also caused a weight loss of roughly 22 percent (as interpreted from a graph) after six months in genetically obese rats.

    It is also worth noting that there was almost no difference in weight in these genetically obese rats after alpha lipoic acid had been given for 3 months. For some reason the weight loss effect did not occur until the the second three months of treatment.

    Increases Calories Burned By 36-50 Percent

    Alpha lipoic acid increased calories burned by roughly 36 percent (as determined from a graph) compared to control animals who were eating more food, and 50 percent compared to pair-fed animals that were fed the same amount of calories as were eaten by the animals given alpha lipoic acid.

    Alpha Lipoic Acid increases metabolism

    Effect Not Due To Toxicity

    The researchers showed that the weight loss-, and appetite-reducing effect of alpha lipoic acid was not due to any toxic effect.

    Reduces Blood Sugar And Insulin

    There was a decrease in blood sugar, insulin levels, free fatty acids and leptin levels in rats given alapha lipoic acid as 0.5 percent of the weight of their food (roughly 5,000 mg per day for human—a huge dose).

    Dose: 0.25%, 0.5%, And 1% of Food; Roughly Equal to 2,500 mg, 5,000 mg, 10,000 mg per Day

    The doses tested were 0.25 percent of food eaten (by weight), 0.5 percent of food, and 1 percent of food.

    Since humans eat roughly 1 kilogram of food per day (1,000 grams), the equivalent doses in humans would be 2,500 mg (0.25 percent of diet), 5,000 mg (0.5 percent of diet), and 10,000 mg per day (1 percent of diet).

     

    Caution: Do not take this much alpha lipoic acid. This would be a huge dose for a human. The dose recommended by Bruce Ames, PhD, researcher from the University of California Berkeley, is 200 mg twice a day for a total of 400 mg. I do not know if studies have been done to determine the safety of higher doses on humans.

    The interview with Bruce Ames about alpha lipoic acid and acetyl-L-carnitine can be found here.

    No Harmful Effects

    Alpha-lipoic acid did not cause any harmful effects. There were no adverse effects on internal organs, blood cell count, or blood chemistry.

    Alpha Lipoic Acid’s Effect on Appetite Not Due to Taste Aversion

    The reduction in appetite from alpha-lipoic acid was not caused by taste aversion either.

    Powerful Antioxidant

    Alpha-lipoic acid is a powerful antioxidant.

    Essential Cofactor For Mitochondrial Enzymes

    Alpha-lipoic acid is an essential cofactor of mitochondrial respiratory enzymes.

    Mitochondria are “cellular powerplants” in cells that help produce the universal energy molecule adenosine triphosphate, also known as ATP.

    TECHINICAL INFORMATION

    For those of you interested in the techincal aspects of how alpha lipoic acid reduces appetite and increases energy…

    Effect Due To Suppressing Hypothalamic AMP-activated Protein Kinase

    Alpha lipoic acid decreases food intake and increases energy expenditure by suppressing hypothalamic AMP-activated protein kinase.

    AMP-activated protein kinase acts as a fuel sensor in the cell and is activated when cellular energy is depleted.

    This study found that hypothalamic AMP-activated protein kinase is important in regulation of food intake and energy expenditure.

    It is also worth noting that injecting glucose (sugar) intravenously into the brain also reduces hypothalamic AMP-activated protein kinase (which decreases appetite), and giving a drug which blocks sugar metabolism increases hypothalamic AMP-activated protein kinase (which increases appetite).

    Increases UCP-1 In BAT

    Alpha Lipoic Acid increases uncoupling protein-1 (UCP-1) in brown adipose tissue (brown fat), indicating that weight loss is partly due to an increase in metabolism.

    Does Not Depend on Leptin, or Affect Neuropeptides

    The researchers determined that the appetite-reducing effect of alpha lipoic acid does not rely on leptin.

    They also determined that alpha lipoic acid does not affect levels of neuropeptides known to affect appetite such as neuropeptide Y, corticotropin releasing hormone, pro-melanin concentrating hormone, or hypocretin (also called orexin).

    Decreases Fat Oxidation

    Stimulation of AMP-activated protein kinase increases oxidation of fatty acids. Therefore, alpha lipoic acid decreases fatty acid oxidation.

    REFERENCE

    Kim M, Park J, Namkoong C, Jang P, Ryu J, Song H, Yun J, Namgoong I, Ha J, Park I, Lee I, Violett B, Youn J, Lee H, Lee K. Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic amp-activated protein kinase. Nat Med. 2004 Jun 13,

    AUTHOR CORRESPONDENCE:

    Ki-Up Lee
    Department of Internal Medicine
    University of Ulsan College of Medicine
    138-736 Poongnap-dong, Songpa-ku
    Seoul 138-736, Korea
    .(JavaScript must be enabled to view this email address)

    Note: Most of the authors were from Korea, however, one of the authors works at the University of Southern California.

    Jang Hyun Youn
    Department of Physiology and Biophysics
    University of Southern California Keck School of Medicine
    1333 San Pablo St. MMR626
    Los Angeles, CA 90089, USA

    Articles on the same subject can be found here:


    COMMENTS

    On Mar 28, 2008 at 2:40 pm Kara wrote:

    . . . . .

    Rodents mainly have brown fat cells, while humans have white fat cells (except for babies). Was this study referring to effect on white or brown fat cells?

    On Mar 28, 2008 at 3:05 pm Larry Hobbs wrote:

    . . . . .

    The study found increased UCP-1 in both brown fat and white fat, but noted, as you also noted, that:

    "Uncoupling protein-1 (UCP-1) in brown adipose tissue is a chief regulator of energy expenditure in rodents."

    -- page 2, col 2

    -------

    However, here was my experience.

    I used to take plain Alpha Lipoic Acid (RS-Lipoic Acid).

    I switched to the more potent R-Lipoic Acid (250 mg).

    The first several days while playing basketball I felt a tremendous amount os stimulation and sweating, but after a few days, I felt a lack of energy and I could not get a sweat going.

    When I looked it up, it turns out that Lipoic Acid inhibits the enzyme that converts the storage form of thyroid hormone ( T4 ) into the active form ( T3 ).

    Therefore, I believe that it reduced my energy level and sweating by decreasing levels of T3 thyroid hormone.

    I am not careful not to take too much, and only take maybe 50 mg -- maybe even less -- once a day, and avoid taking it before exercise because it DECREASES my energy levels.

    Therefore, based on my experience, I do not believe that alpha lipoic acid will cause weight loss in humans and may even slightly have the opposite effect.

    On Mar 29, 2008 at 2:13 am Kara wrote:

    . . . . .

    Its interesting to note your observations. However, do you believe it really was the effect of only 250mg Lipoic Acid in a short span of a few days? In my view, it sounds unlikely.

    Did you have blood/urin/thyroid tests done before and after taking Alpha Lipoic acid to determine whether it had these effects? Don't you believe you would require a more long-term use to be able to observe actual effects from an intake of supplements?

    Even vitamins in large dosage don't give effect in short use but is gradual and require long-term usage. In what dosage and for how long period of time in consuming Alpha Lipoic does it take to decrease levels of T3 thyroid?

    Botox,f.ex., has been said to actually destroy anti-oxidants and age people faster - but this may be related to long-term use and with a certain dosage level.

    On Mar 29, 2008 at 11:13 am Larry Hobbs wrote:

    . . . . .

    Kara,

    No, I did not have my thyroid levels checked when taking R-Lipoic acid to see if it lowered levels of T3.

    Here is how I know it was the R-Lipoic acid.

    -------

    Correction : 100 mg of R-Lipoic Acid, not 250 mg

    CORRECTION : I switched from taking 250 mg of RS-Alpha Lipoic Acid to taking 100 mg of R-Lipoic Acid.

    CORRECTION : I now take only maybe 20 mg of R-Lipoic Acid per day.

    ------

    Here's how I know it was the R-Lipoic acid.

    I took it and had a tremendous increase in energy, aggression and sweating during basketball for a few days.

    Then, after a few days, I had a tremendous decrease in energy, aggression and sweating. I had no energy. I could not get a sweat going.

    When I found out it decreases T3, I took some T3 which I already had ( Cytomel ).

    The T3 helped some, but did not get me back to even a normal amount of energy.

    My energy levels returned to normal when I stopped the R-Lipoic Acid

    So I stopped the R-Lipoic Acid and my energy and sweating returned to normal immediately.

    To this day -- 7.5 years after switching to R-Lipoic acid -- I notice that if I take slightly too much R-Lipoic acid before exercise, and I am only talking about taking maybe 40 mg -- I feel a lack of energy during exercise.

    To avoid this, I take the R-Lipoic acid in the morning and avoid taking it in the afternoon before playing basketball or tennis.

    -----

    I've taken Armour Thyroid for 20+ years

    I have taken natural desiccated Armour thyroid for 20+ years. It contains both T4 and T3.

    I've experimented with higher doses and lower doses, so I know what it feels like.

    I also have experimented with taking T3 on and off for probably 10 years.

    -----

    Too much R-Lipoic Acid makes my hands cold

    If I take too much R-Lipoic acid, my hands get cold.

    I can correct this, that is warm up my hands, by taking some T3.

    -----

    I've taken handfuls of supplements for 26 years.

    I would guess that I have spent in excess of $50,000 on supplements in that time.

    I've had many odd experiences.

    I have often thought, "It couldn't possibly be this new supplement that I am taking that is making me feel this way, could it?"

    But it has almost always turned out that it was the supplement.

    On Jun 07, 2011 at 7:11 pm gary Langley wrote:

    . . . . .

    I am at present taking 1500mg of Gabapentin for the beginning of Diabetic Neuropathy but I am only slightly high in glucose readings...I still get a pain in my toe almost once a day. Will R Alpha Lipoic Acid halp to control any Neuropothy pain in my toe (not gout)...Thanks, Gary Langley

    On Jun 08, 2011 at 5:56 pm Larry Hobbs wrote:

    . . . . .

    Gary,

    Sorry, but I don't know if R Lipoic Acid will help or not.

    Larry Hobbs

    On Jun 17, 2011 at 4:09 pm Gary Langley wrote:

    . . . . .

    By taking just Gabapentin throughout the day (1800mg} I still got substantial one to two minute stabs of hard pain in my left big toe about 4 or 5 times a day I am just barely prediagetic. My neuralogist after electric and blood tests gave me

    a diagnosis of Diabetic Peripheral Polyneropothy. With all that Gabapentin, I still woke up about 3 AM from a stabbing pain in my toe. I added 300mg of R-Alpha Lipoic Acid and a multi B vitamin to my dosage 4 hrs before bedtime plus my usual 600mg of

    Gabapentin at bedtime and have slept through the night since. My Neurologist won't respond to my inquiry if mixing Gabapanetin with R-Lipoic Acid could have any negative side effects. does anyone have any experience with this or similiar scenarios? Thanks, Gary Langley

    On Jun 17, 2011 at 6:38 pm Larry Hobbs wrote:

    . . . . .

    Gary,

    Interesting.

    I find R-Lipoic Acid stimulating (as well as regular Alpha Lipoic Acid.)

    I avoid taking it too late in the day because it keeps me awake.

    I will post a separate posting about lipoic acid and neuropathy.

    Larry Hobbs

    On Jun 17, 2011 at 6:43 pm Larry Hobbs wrote:

    . . . . .

    Gary,

    There are published articles about Lipoic Acid and Neuropathy.

    Go to PubMed.com.

    Search for "lipoic acid neuropathy".

    For example, the 9th paper -- Vallianou et al, 2009, with the abstract shown below -- notes that:

    "Alpha-lipoic acid seems to delay or reverse peripheral diabetic neuropathy through its multiple antioxidant properties.

    "Treatment with alpha-lipoic acid increases reduced glutathione, an important endogenous antioxidant.

    "In clinical trials, 600 mg alpha-lipoic acid has been shown to improve neuropathic deficits."

    ---------

    You can download the paper for free.

    ---------

    Rev Diabet Stud. 2009 Winter;6(4):230-6. Epub 2009 Dec 30.
    Alpha-lipoic Acid and diabetic neuropathy.

    Vallianou N, Evangelopoulos A, Koutalas P.

    Source

    Department of Internal Medicine, Polykliniki General Hospital, 3 Pireos Str., 10552 Athens, Greece.

    Abstract

    Diabetic neuropathy presents a major public health problem.

    It is defined by the symptoms and signs of peripheral nerve dysfunction in diabetic patients, in whom other causes of neuropathy have been excluded.

    Pathogenetic mechanisms that have been implicated in diabetic neuropathy are:

    a) increased flux through the polyol pathway, leading to accumulation of sorbitol, a reduction in myo-inositol, and an associated reduced Na+-K+-ATPase activity, and

    b) endoneurial microvascular damage and hypoxia due to nitric oxide inactivation by increased oxygen free radical activity.

    Alpha-lipoic acid seems to delay or reverse peripheral diabetic neuropathy through its multiple antioxidant properties.

    Treatment with alpha-lipoic acid increases reduced glutathione, an important endogenous antioxidant.

    In clinical trials, 600 mg alpha-lipoic acid has been shown to improve neuropathic deficits.

    This review focuses on the relationship of alpha-lipoic acid and auto-oxidative glycosylation.

    It discusses the impact of alpha-lipoic acid on hyperglycemia-induced oxidative stress, and examines the role of alpha-lipoic acid in preventing glycation process and nerve hypoxia.

    ------

    I would download and read the entire paper.

    Don't worry about the stuff you don't understand.

    Larry Hobbs

    On Jun 18, 2011 at 8:26 am Gary Langley wrote:

    . . . . .

    Thanks Larry for your input and research..I have also read many articles on the benefits of R-Alpha Lipoic Acid. What I can't find, is anything about taking Gabapentin and Alpha Lypoic Acid within hours of each other to relieve my nght time pain. I am concerned about the chemical reaction to each in my body..Thanks, Gary

    On Jun 18, 2011 at 8:58 am Larry Hobbs wrote:

    . . . . .

    Gary,

    Drugs[dot]com says:

    "There were no interactions found in our database between Alpha Lipoic Acid and gabapentin"

    http://www[dot]Drugs[dot]com/drug-interactions/alpha-lipoic-acid-300-with-gabapentin-2574-15177-1147-0.html

    ---------

    A paper on PubMed also does not mention any problems giving the two items together.

    See here:

    http://www.ncbi.nlm.nih.gov/pubmed/18403218

    and here:

    http://www.ncbi.nlm.nih.gov/pubmed/20711135

    -------

    I doubt that there is an interaction between Gabapentin and R-Lipoic Acid or else it would have been reported.

    Larry Hobbs

    On Jun 18, 2011 at 10:41 am Gary Langley wrote:

    . . . . .

    Thanks Larry, for your info on the BMS blind study. That is very encouraging and relieving. Although they mention Alpha Lipoic and not R-Alpha Lipoic. Two different substances, I have already read the other article about treating Neuropathy, but it did not combine the two substances combined. I have read articles on the effects to the organs on each and the side effects of each. But this is the first article addressing combining the substances. Again, Thank you :>)

    On Jun 18, 2011 at 12:25 pm Larry Hobbs wrote:

    . . . . .

    Gary,

    I think that R-Lipoic Acid is simply one-half of Alpha Lipoic Acid, which is RS-Lipoic Acid which is essentially R-Lipoic Acid plus S-Lipoic Acid.

    I consider them to the same -- both being Lipoic Acid -- except that you only have to take one-half as much R-Lipoic Acid as Alpha Lipoic Acid (RS-Lipoic Acid).

    Larry Hobbs

    On Jun 18, 2011 at 6:58 pm Gary Langley wrote:

    . . . . .

    Hi Larry,

    you are correct. Another interesting fact about R-Alpha Lipoic Acid is it should be refrigerated compared to stabalized R-Alpha Lipoic Acid Which doesn't. Type in "The difference between R-Alpha Lipoic Acid and Stabalized R-Lypoic Acid" on your browser and see the difference.

    Gary

    On Jun 18, 2011 at 7:51 pm Larry Hobbs wrote:

    . . . . .

    Gary,

    I have not researched this, so I am just guessing here, but I am skeptical that there is any difference between stabilized and non-stabilized R-Lipoic Acid.

    My guess is that it is nothing more than a marketing ploy to sell stabilized R-Lipoic Acid, and probably at an inflated price.

    I am skeptical of there being any difference.

    The same thing happened with arginine.

    I forget what the claim was, but a girl who held the patent for something to do with arginine, posted a number of articles making some claim that some form of arginine (that she held the patent to) was superior.

    A bogus claim to try and sell product.

    I am skeptical of any claim like this.

    The Life Extension Foundation also promoted R-Dihydrolipoic acid as being superior.

    I bought some and tried it, but it did NOT have the same effect.

    I went back to R-Lipoic Acid.

    Larry Hobbs

    On Jul 14, 2011 at 4:55 pm Gary Langley wrote:

    . . . . .

    Interesting new development...I went in for an endocrynology evaluation and the Dr. said with my Glucose and Hemoglobin stats, it was highly unlikley that I had Diabetic Peripheral Polynueropophy at all...His is sending me in for a

    second opinion from a different neurologist...I have tried adjusting my spine somewhat myself and it has worked...I think it was my golf that was torking my spine and causing the neuropathy in my

    left big toe...I have stopped the Gabapentin altogether and now only take 210 mg of R-Lipoic Acid a day and have no pain...If I have a twinge in my big toe, I simply stand up and twist my shoulders one direction and my hips the other direction a few times and I am fine...Go figure

    Gary

    On Jul 15, 2011 at 8:46 am Larry Hobbs wrote:

    . . . . .

    Gary,

    Excellent.

    Thanks for the update.

    Always good to get a second opinion... and maybe a third and fourth and fifth and sixth.

    I think everyone has tunnel vision depending on what they know or what their area of interest is, such as your neurologist telling you that you had diabetic neuropathy.

    A friend of mine is a young radiologist, and when I have asked him a question for myself or for my parents, he has usually told me that me or my parents should get a CAT scan or an MRI... because that is what his specialty is and that is where his tunnel vision is.

    I think this happens with a lot of psychiatrists also, where they tend to think that everyone with a problem who walks through their door is depressed and needs an antidepressant.

    Larry Hobbs

    On Jul 15, 2011 at 10:52 am Gary Langley wrote:

    . . . . .

    Thanks...You are right...Yes, Doctors are only human and make mistakes like all others do...If a doctors' ego is too fragile for second opinions, then they are too immature to practice medicine...Our health is our responsability...A doctor is just one of our employees to help with that responsability...I hope life is treating you well.

    Gary

    On Jul 15, 2011 at 11:19 am Larry Hobbs wrote:

    . . . . .

    Gary,

    I agree completely.

    Also, no one likes to admit to making mistakes, including doctors.

    In fact, doctors may be even more resistant to admitting mistakes because they may be afraid that:

    1. Patients will lose respect for them.

    2. Patients may leave them and go to another doctor.

    3. Patients may sue them.

    So, unfortunately, I think many doctors may make a diagnosis or prescribe a drug for blood pressure or cholesterol or diabetes or depression or anxiety or sleep or bone-building or neuropathy, as in your case, and then are unwilling to admit that they were wrong, so people end up taking something that is doing them more harm than good.

    And I agree that the doctor works for YOU.

    You are the boss, NOT the doctor.

    I also believe that most, or practically all, decisions a doctor makes when it comes to treating patients involve the doctor doing what will protect them from a lawsuit.

    My guess is that most people are not aware of this or never think about this.

    I think A LOT of people are given blood pressure drugs and cholesterol drugs and diabetes drugs, etc that they DO NOT NEED, however, their doctor has given it to them because they are trying to protect themselves from a lawsuit in case something happens to the patient, such as a heart attack or stroke, etc.

    I wish there doctors had an open discussion with patients about this and said, "Look, I don't think you need to take these blood pressure drugs or cholesterol drugs or diabetes drugs, but the guidelines, which are written by researchers who are paid by the drug companies, suggest that I should give you these drugs. And I don't want to get sued, so if you want to take my advice and NOT take these drugs, which I DON'T think you need, I'd like you to sign a Consent form which says that I discussed this with you."

    Larry Hobbs

    On Jul 17, 2011 at 5:49 pm Gary Langley wrote:

    . . . . .

    Larry...You hit the nail squarely on the head...Follow the money...How come there are 50 million Americans without health care in the richest industrialized nation in the world? This is not the country I knew in the 40's thru the 70's..

    Gary

    On Jul 17, 2011 at 9:22 pm Larry Hobbs wrote:

    . . . . .

    Gary,

    I agree.

    Unfortunately, I don't trust drug companies any more.

    I don't trust the research any more either.

    They only publish what helps them sell more drugs, and bury the rest.

    They only "hire" / pay the researchers who help them to sell more drugs.

    It's not about science and truth any more.

    It's only about selling more drugs.

    I encourage everyone to read the wonderful book "Influence" by Prof. Robert Cialdini who has been studying the topic of influence for something like 35 years.

    I've read it several times and am going to read it several more until I know it forwards and backwards.

    If you read it, think about how each topic affects your doctor and researchers who do research for the drug companies.

    You can also check to see if your doctor has been paid by the drug companies by going to http://www.propublica.org and click on "Dollars for Doctors" at the top.

    One of my mother's doctors was paid $40,000 by the drug companies.

    No one can EVER convince me that this does not influence what the doctor prescribes.

    Sam Walton, the founder of Walmart, would not let his purchasing agents accept even a handkerchief because he knew it would affect their buying decisions.

    What would Sam Walton would say about University researchers being paid tens of thousands or hundreds of thousands of dollars by the drug companies.

    What would Sam Walton would say about scientists from the US National institutes of Health (NIH) accepting tens of thousands or hundreds of thousands of dollars by the drug companies?

    What would Sam Walton say about the fact that 8 of 9 people on the National Cholesterol Education Program who came up with the national guidelines for cholesterol and who should take drugs had been paid by the drug companies?

    Do you think this affected what they recommended?

    Yes, of course it did!

    The same is true for the research and guidelines for blood pressure, diabetes, depression, etc.

    It is a shame.

    I don't believe any of it any more.

    I also encourage people to watch the documentary "Inside Job" about the financial crisis.

    The filmmaker interviews many of the top economists from famous universities like Columbia University in New York City who wrote all kinds of crazy things before the financial crisis, and he reveals how they were paid by the investment banks such as Goldman Sachs, JP Morgan, Morgan Stanley, etc.

    They wrote things that were completely wrong, and looking back, sound completely ridiculous, and I can't imagine anyone with half a brain could write such things.

    And when he interviews them and asked one of them something like, "Why did you write this? Why didn't you reveal that you had been paid $124,000 by the Iceland Chamber of Commerce when you wrote that Iceland was a great place to invest, shortly before the had a financial collapse?"

    Of course, the some very famous guys who wrote this crap defend what they did, and said, "Well, everybody believed it at the time." or "Well, you just go with the best information you have."

    If you watch it, think about how it is EXACTLY THE SAME with university drug researchers, and the scientists from the National Institutes of Health.

    I don't believe the research any more.

    I don't believe the guidelines on cholesterol or blood pressure or diabetes or depression or anything else any more.

    It's nothing more than sales literature to help the drug companies sell more drugs.

    Unfortunately, most doctors are NOT aware of this, and instead assume that if a paper comes from some guy are Harvard or Yale or MIT or any from the National Institutes of Health, it must be scientific truth. NOT TRUE!

    Buyer beware.

    My eyes have been opened in the last 3.5 years, since the beginning of 2008.

    Larry

    On Jul 18, 2011 at 9:57 am Gary Langley wrote:

    . . . . .

    You certainly have good cause to have your opinion...Thanks for the tip on the book...Good to keep aware and think on your own two feet...Gary

    On Jul 18, 2011 at 9:59 am Larry Hobbs wrote:

    . . . . .

    Gary,

    Thank you.

    Larry Hobbs

    Please feel free to share your comments about this article.


    Name:

    Email:

    Comments:

    Please enter the word you see in the image below:


    Remember my personal information

    Notify me of follow-up comments?



    © Copyright 2003-2021 - Larry Hobbs - All Rights Reserved.