Oct 19, 2015 • By Yogesh Giri •
Branched Chain Amino Acid Supplements are considered as one of the best way for improving the bodybuilding in the fitness community. Branched Chain Amino Acid Supplement support more health benefits comparing to the other supplements available in market. BCAA supplementation is especially used for maintaining the gain mass and maintaining the muscles with the calorie diet. Many bodybuilding competitors uses the supplement for increasing their body muscles with the maximum strength. Although dieting is one of the option for making the body looking awesome but it will not increase the muscle strength with added mass. Dieting is one of the catabolic function so that it will lead to the muscle breakdown so it is better to choose the BCAA supplementary function. Choosing the Branched Chain Amino Acid Supplements or BCAA will be efficient for increasing the better muscle strength than doing the common exercises. Most of the doctors are also recommending this bcaa supplements for the bodybuilders to improve their muscle strength.
Functions Of BCAA Supplements:
The BCAA supplements will normally establish the branched chain of amino acids for stimulating the protein synthesis. BCAA increases the normal synthesis of cellular machinery that is responsible to carry out the protein synthesis process. Therefore, the BCAA not only increase the protein synthesis rate but also increases cell capacity with protein synthesis. BCAA supplement reduces the protein breakdown rate so that it will decrease the breakdown pathway of protein components and also involved with many protein breakdown factor. Taking the BCAA supplements will be the excellent choice for decreasing protein breakdown and increasing protein synthesis. The supplements will intake the better muscle gain or maintenance in the natural methods. The BCAA supplements also have many other positive benefits with the reduction of protein breakdown with the improved workout intensity. Each of the BCAAs supplement will compete with amino acid tryptophan in the entry of brain as tryptophan converted for neurotransmitter serotonin. When doing exercise, the serotonin level will rise and increase of fatigue perception with less intense workout.
Effective Fueling Strategy:
The BCAA supplementation improves the molecular level with the decrease of muscle loss. Normally the muscle loss will occur with the increased protein breakdown for liberating the amino acids in muscles for fuel. When there is more energy intake, then it will reduce the protein synthesis so for fueling the muscle strength, the BCAA supplements are quite efficient for increasing the Muscle mass with the rate of protein synthesis. There is no side effects taking this wonderful supplements and it will give you the best benefits for increasing the body muscles with the heavy workout. You will be amazed with the increased type of muscle mass and there is no need to take any other supplement added as all the effect will be in the protein synthesis. When you are lifting heavy load then it gives better idea that adapts the body system gaining the maximum immune system. Taking the exact dosage of the supplement is most necessary so that it adds increased muscle.
Apr 10, 2012 • By Uriah •
L-Lysine hydrochloride(C6H15ClN2O2) is an essential free-form amino acid and is one of the 20 most common natural amino acids that the body needs for growth and tissue health. This acid is especially good for helping the body fully absorb calcium as well as reducing thesymptoms of herpes simplex infections. It can also be taken to treat common mouth, sores such as canker sores, and other infections. L-lysine HCl is a molecular form of lysine that is more soluble and easier to digest.
Purity and Concentration
This pharmaceutical-grade amino acid contains no fillers, taste additives or anti-caking agents. This is the hydrochloride form of L-lysine. Hydrochloric acid, a naturally occurring stomach acid, helps break up fats and proteins for quicker digestion in the small intestine and makes the absorption of nutrients through the walls of the intestines easier.
Like all amino acids, lysine primarily acts and functions as a building block for proteins. It's also a key player in the production of various enzymes, hormones and antibodies and plays a major role in calcium absorption. When works with other essential amino acids, L-lysine HCl can maintain the body's store of nitrogen and is found many sports and bodybuildingsupplements. Bodybuilder, weightlifters and other strength athletes are also using L-lysine in their training regimens because of its role in developing muscle protein.
Lysine is needed to produce carnitine, another amino acid which helps to convert fatty acids into energy. It is also a vital amino acid for growth. The most well-known use for lysine hydrochloride is as an effective treatment for the herpes simplex virus. This virus manifests with painful sores of the mouth, commonly referred to as cold sores. It is believed that lysine helps control these conditions by inhibiting the strength of another amino acid, arginine, which can contribute to the appearance of cold sores. Lysine hydrochloride works to inhibit the production of the herpes simplex virus by slowing, if not eliminating, the effects of the virus.
L-lysine hydrochloride(CAS number 657-27-2 ) helps produce antibodies, assists in proper tissue growth and is needed for synthesizing proteins. Good sources of lysine are foods rich in protein including meat (specifically red meat, pork, and poultry), cheese (particularly parmesan), certain fish (such as cod and sardines), nuts, eggs, brewer's yeast, legumes, soybeans (particularly tofu, isolated soy protein, and defatted soybean flour), spirulina and fenugreek seed.
The soy-based products are particularly beneficial to vegetarians, who may find it hard to get lysine from their diets since vegetables are generally a poor source of lysine, with the exception of legumes (beans, peas, lentils).
Uriah is the freelance writer for e-commerce website in the chemistry. is just a place for you to look for some chemicals! Our guidechem provide the most convenient conditions for the international buyers and let these leads benefit all the business people.
Oct 11, 2009 • By Chris Soares •
BCAA stands for Branch Chained Amino Acids, and it is comprised of Leucine, Valine, and Isoleucine. BCAAs are the main amino acids oxidized during exercise, and due to them totaling 1/3 of the total amino acids in muscle tissue it is important to ingest enough of these during exercise. Additionally, they are the building blocks of muscle, so they are very important to intake. Furthermore, these are essential amino acids which means we need to have them in our diet, but luckily whey protein has a high content of BCAAs.
L-Leucine; is it the most important amino acid?
This amino acid is probably the most important out of the three, as research indicates that during intense exercise is used up quickly compared to the others. One study compared muscle protein turnover after resistance exercise (1). They had three different groups: carbohydrates only, protein and carbohydrates, and finally leucine carbohydrates and protein. Their findings were interesting to say the least as the leucine+carbohydrates+protein group had the largest whole body proteinbalance. Furthermore they explained that it could have been caused from various different pathways such as providing more amino acids for muscle protein synthesis, the leucine increased insulin concentrations when compared to the other groups which could help in protein synthesis (1). They also found that leucine has the ability to help stop protein degradation, which they believe is caused by greater insulin secretion (1). Furthermore, another study found that leucine supplementation stimulates recovery of the skeletal muscle protein synthesis after exercise. However, they used rats in the study but the results are still interesting (2).
BCAA supplementation shown to decrease DOMS and protein degradation!
Another study went over BCAA supplementation on delayed onset muscle soreness (DOMS) and muscle fatigue caused by squats in human. Their results showed that supplementing with BCAAs before squats caused a decrease in DOMS and muscle fatigue (3). Additionally, another study found that exercise causes BCAA degradation, so during resistance training the need for BCAAs goes up (4). Finally they found that supplementing with BCAAs before and after exercise can aid in promoting skeletal muscle synthesis, and also reduce exercise induced muscle damage (4). Overall BCAAs can be a very important supplement and they have a lot of research backing their effectiveness. I think they would work very well during weight loss because it could help decrease DOMS which can limit exercise during caloric deficits. Furthermore they can help stop protein degradation, which too would be good when you are trying to save your precious muscle while losing that fat.
1. Gorselink, Marchel, Rene Koopman, Hans Keizer, et al. "Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects." Journal of Applied Physiology. 288 (2004): E645-653. AJP - Endocrinology and Metabolism. <http://ajpendo.physiology.org/cgi/content/full/288/4/E645#R32>.
2. Anthony, Joshua C., Tracy G. Anthony, and Donald K. Layman. "Leucine Supplementation Enhances Skeletal Muscle Recovery in Rats Following Exercise." Journal of Nutrition 129 (1999): 1102-106. The Journal of Nutrition. <http://jn.nutrition.org/cgi/content/abstract/129/6/1102?ijkey=5ae97f64f5885bebe68276f837286c20ff4670cf&keytype2=tf_ipsecsha>.
3. Mawatari, K., H. Kobayashi, N. Shimomura, et al. "Nutraceutical effects of branched-chain amino acids on skeletal muscle." Journal of Nutrition 136 (2006): 529S-32S. PubMed. <http://www.ncbi.nlm.nih.gov/pubmed/16424141?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_Discovery
4. Harris, RA., M. Nagasaki, Nakai N., et al. "Exercise promotes BCAA catabolism: effects of BCAA supplementation on skeletal muscle during exercise." Journal of Nutrition 134 (2004): 1583S-587S. PubMed. <http://www.ncbi.nlm.nih.gov/pubmed/15173434?ordinalpos=itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.
Jul 20, 2009 • By Mike Didcky •
There’s so much talk about treating anxiety with medications like Xanax and Valium but often times something as simple as an amino acid supplement can do the trick. Taurine is an amino acid which plays a major role in the brain as an "inhibitory" neurotransmitter & neuro-modulator and is similiar in structure to the amino acids GABA & L-Glycine, which act to calm or stabilize an excited brain. Taurine acts by regulating the sodium & potassium concentration in the cells & the magnesium level between the cells which all control the electrical activity of the cells & communication between cells. Thus, taurine also has anti-anxiety & anti-convulsant activity; it has also been found useful in some cases of migraine, insomnia, restlessness, irritability, alcoholism, obsessions, depression, hypomania or mania.
The total ideal body pool of taurine for adults is 12,000- 18,000 mg. Something to be aware of: since taurine also affects the hypothalamus to help regulate body temperature, higher doses can decrease your temperature & give a senses of chilliness. Taurine also plays a role in memory & increases the level of a memory neurotransmitter, acetylcholine, in the brain (in animal studies).
Where do you get taurine from? Taurine is highly concentrated in animal & fish protein or organ meats so strict vegetarians can be at risk for taurine deficiency. Your body can make taurine in the liver and brain from the amino acids, L-Cysteine and L-Methionine and the three enzymes involved in the conversion, all need the pyridoxal-5-phosphate form of Vitamin B6 for this conversion. So make sure you take your vitamins if you have anxiety too! Also, females tend toward lower taurine levels than males so it is especially important for the ladies to get proper nutrition. Aim for a proper balance of whole grains, organic vegetables and fruits, nuts and seeds and dairy and poultry a few times a week for balanced nutrition.
Nov 16, 2014 • By Wendy •
the eight B vitamins. It is a water-soluble vitamin relates to the normal functioning of brain and nervous system and the formation of blood. Vitamin B12 is proved to be involved in the metabolism of every cell of the human body, especially affecting DNA synthesis and regulation, and also fatty acid metabolism and amino acid metabolism.
Some evidences show that vitamin B12 may help lower blood level of a substance called homocysteine which is closely related to heart disease and stroke. One analysis of several studies found folic acid cut down homocysteine level by about 1/4 and when folic acid was combined with vitamin B12, homocysteine level was found declined by another 7%, according to an article published in the Journal of the American Medical Association in 2002.
Since homocysteine levels can be lowered with folic acid and vitamin B12 supplements, some scientists start to assume that these vitamins could also work to reduce the risk of memory loss and Alzheimer's disease. But a recent study indicates that taking vitamin B12 and folic acid supplements may not reduce the risk of memory and thinking problems.
This study was published online in the US journal Neurology. Test Subjects of involved in this study are these with high blood levels of homocysteine which is linked to memory loss and Alzheimer's disease. Those 2,919 subjects involved are old people with an average age of 74. They were respectively asked to take a tablet with 400 micrograms of folic acid and 500 micrograms of vitamin B12 or a placebo every day for two years. And their memory and thinking skills were tested at the beginning and end of the study.
The result showed that the homocysteine level of the group of people taking vitamin B12 decreased by more than the group taking the placebo. However, when it came to the thinking and memory ability, there was no big difference between the two groups.
This research has overthrown the results of early studies which shows taking folic acid and vitamin B12 may be beneficial to human's thinking and memory skills. Can Vitamin B12 really reduce the risk of memory loss? This still remains a question needed to be further studied
Homocysteine is a non-protein α-amino acid. And it is also one of the 20 amino acids in the world, which are molecules that the body requires to synthesize all body proteins. And its reaction occurs usually with the help of vitamin B6, vitamin B12 and folic acid.
This work is contributed by Wendy Kally from Creative Bioarray, a well-recognized biotech company providing the highest standard quality research products and services.
Sep 09, 2015 • By Geeta Patel •
Chlorophyll is stored solar energy. You can even call chlorophyll as the green blood of plants which provides human beings with more red blood cells.
Image Credits: lytnyc
"German nutrition pioneer Halima Neumann claims that chlorophyll is the only nutrient that can transfer stored solar energy from plants to the cells of the human body. Solar energy becomes life energy, Chi, life-force."
The electric green color of Japanese Matcha is due to its high chlorophyll content in it. Matcha being chock full of chlorophyll removes heavy metals like - mercury, lead and others and other harmful chemicals from our bodies.
Japanese Matcha is just 100% pure shade-grown green tea leaves flooded with ridiculous amount of phytonutrients and minerals. It consists of more antioxidants by weight than any food. It is also packed with oodles of amino acids. Hence, Matcha is also called as the Iron Man of super foods, as many researches has revealed multiple advantages of green teaand the potential of this brew in battling diabetes, carcinogens, high blood pressure, obesity, GI distress, and even bad breath.
Health Benefits Of Chlorophyll in Matcha
Chlorophyll as Oxygen Carrier and Quick Healer:
Chlorophyll in Matcha acts as a cleanser that helps our body to keep itself healthy. Chlorophyll helps our body in the following ways-
- It de-acidifies and mineralizes the environment of cells.
- It helps to restore the acid-base balance.
- Normalizes the pH-value of our body.
- Chlorophyll disinfects and supports the immune system.
- It is an excellent deodorant and removes bad odors.
- It transports oxygen to the cells and helps with the removal of CO2.
- Chlorophyll is particularly known as oxygen carrier, blood cleanser and blood builder. Chlorophyll stimulates detoxification and supports the lymphatic system in its functioning.
Already in 1940, the "Journal of Surgery" reported that in more than 1,200 illnesses, chlorophyll provided faster recovery. Viktoras Kulvinskas (co-founder of the Hippocrates Institute, nutrition expert) also emphasized the curative affect of chlorophyll. In his book, Survival in the 21st century, Viktoras Kulvinskas says that there is no quicker and safer way to regulate digestion and to ensure cell regeneration than with chlorophyll.
Protection Against Radioactivity:
Although our body has the capacity to heal itself, in this day and age where there is mounting exposure to harmful radiations, drinking Japanese Matcha helps to support our immune system. Chlorophyll in this green brew has anti-mutagen and anti-carcinogen qualities. Chlorophyll, EGCG and high ORAC values in it help to make free radicals harmless. In addition, the chlorophyll content binds toxic radiation particles and eliminates them, thus, protecting your body is against certain forms of radiation.
Chlorophyll for Detoxification:
As mentioned above Chlorophyll absorbs heavy metals, chemical toxins, odors and radiation and eliminate them. Ordinary green tea brewing involves infusing leaves into the water and at the time of drinking the leaves are thrown away. But in case of Matcha as the tea leaves are ground to a powder, you ingest the whole leaf. Thus you get the wholesome goodness of chlorophyll content which is many times higher than in other green teas.
So, grab a Japanese Matcha today to reap all the advantages of Chlorophyll content in it.
Irritable Bowel Syndrome with Diarrhea (IBS-D) Drugs Market Size, Application Analysis, Growth Trends and Forecasts 2015 – 2022 - Credence Research
Apr 04, 2016 • By Ainsley Lewis •
The latest market report published by Credence Research, Inc. "Global Irritable Bowel Syndrome with Diarrhea (IBS-D) Market – Growth, Share, Opportunities, Competitive Analysis, and Forecast, 2016-2022," the irritable bowel syndrome with diarrhea (IBS-D) drugs market was valued at USD 289.3 Mn in 2015, and is expected to reach USD 1,115.06 Mn by 2022, expanding at a CAGR of 13.89% from 2016 to 2022.
Browse the full report Irritable Bowel Syndrome with Diarrhea (IBS-D) Market – Growth, Share, Opportunities, Competitive Analysis, and Forecast, 2016–2022 report at:
Recent approvals for two new prescription drugs to treat irritable bowel syndrome with diarrhea (IBS-D) have become the biggest phenomenon in the IBS-D drugs market. These approvals are viewed as breakthrough step in the long struggle to discover effective treatment for IBS-D.
Viberzi (eluxadoline) assists in controlling bowel contractions thus containing diarrhea, whereas Xifaxan (rifaximin) is an antibiotic that treats diarrhea by altering the gut flora. Xifaxan had been used off label for treating IBS-D, thus direct approval for treating IBS-D will lead to growth in demand for Xifaxan during the forecast period. Drugs such as loperamide will experience a slack in demand due to the introduction of the said novel drugs.
Geographically, North America is the largest market for IBS-D drugs. Higher awareness about the disease, expected prompt availability of the newly approved drugs, better reimbursement system and higher IBS prevalence are the prime factors that drive the IBS-D drugs market in North America. On the other hand, Asia Pacific is expected to be the fastest growing regional market for IBS-D drugs. It is estimated that Asia Pacific market will progress at a CAGR of approximately 17% during the forecast period 2016-2022. Japan with its largest pool of geriatric population and with the anticipated approval for Xifaxan in 2018 makes the country the largest national market in Asia Pacific region. In addition, it is also estimated that due to factors such as moderate purchasing power in the patient population, lower diagnosis rates and poor disease awareness will contribute to sustained demand for OTC IBS-D drugs in the region. Regions such as Latin America and MENA are believed to follow the trends in Europe and North America market.
Commenting on the competitive scenario, the IBS-D drugs market is fragmented with no clear leader in terms of market revenue share. However, it is expected that with gradual approvals in the international markets, Valeant (Salix Pharmaceuticals) will emerge the market leader in the overall IBS drugs market with products for both IBS-D and IBS-C treatment.
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Mar 06, 2007 • By Chung Leong Yu •
Eating muscle building foods does help you get the edge and build muscles much faster than just eating normal foods. Muscle building foods that is refereed here is not some engineered freak food, it just carefully selected natural foods that contain high in protein that can help you accelerate your muscle building process. Building muscle is not as simple as just hopping into the gym, lift a few weights and you will get results. It requires much more than that. Number one, you need an excellent workout plan and then, you need a solid diet. Just imagine you are a homebuilder, even with the best tools and blue print, you cannot build if you do not have enough cement.
You get results from your workout when you rest, not when you are working out. During your workout, you are tearing your muscle in microscopic scale, and your muscles will recover and grow bigger when you feed them with muscle building foods like protein. You cannot get big muscles by just eating bread and beans. You need foods that contain complete amino acid profiles.
You have to include these power muscle building foods in all your meals. Consuming them bit by bit, spread throughout the day can increase the absorption rate of these foods in you body. Eating a large portion at once will not work because your body cannot absorb all the nutrients at once. Here are mini lists of muscle building foods that can help you build lean muscle that is rock solid in no time!
Muscle Building Foods 1
Beef is an all time favorite in a body builders diet. Roughly, 100 grams of beef contains 30 grams of high quality protein. These proteins are high BV protein, which means that, if you consume 100 grams of steak, 30 grams of protein will be absorbed by the body and utilized for protein synthesis. The steak, which contains the highest protein, is the Silverside lean. This is a good choice of steak because it also contains very low fat, 5 grams of fat only. There are many ways you can cook beef. The best way to do it is to roast it because this way of cooking uses very little oil. For a quick meal you can also buy beef strips and stir fry it with vegetables, onions and chili using olive oil.
Muscle Building Foods 2
Famous body building food number two is the all time favorite, eggs! Eggs are such a power food for building muscles because it the eggs whites contain no fat and although the egg yolk is high in cholesterol, it provides Omega 3, which is good fats. Eggs are also a source of protein, which contains a complete amino acid profile. Eggs are very easy to get, dirt cheap and convenient to bring around. One egg contains 6 grams of protein, 3 grams in the yolk and 3 grams in the white. There are tons of ways to cook eggs. The best way to cook eggs for dieting is to cook in hard boil or half boil, then eat it with a bit of soy sauce, this is good method of cooking because it contains low fat. To kick out of the boredom, make scrambled eggs with olive oil and chili.
Muscle Building Foods 3
Another fantastic lean source of protein is poultry. Chicken and turkey is a very good source of protein, low in fat, cheap and easily attainable. Although some parts of the chicken are high in fat, like the thigh, it is ok to eat it if you take the skin. 100 grams of chicken can give you 30 grams of high quality protein. The good thing about poultry is that it taste really good in sandwiches, salads, roast as well as stir fried.
Muscle Building Foods 4
When your parents say, eat your fish, they are right. Fish is also a powerful muscle building food because it is low in fat, high in protein and high in omega 3. Although fish is slightly more expensive that the other sources, having fish twice a week is good enough. The fishes that are high in protein are lobster, haddock, mullet and saithe. If you want convenience, go for tuna fish. Tuna fish is also very high in protein; a can of tuna can easily supply you with 30 grams of protein. Tuna have become a more desirable choice because it can be use with sandwiches, salads and other dishes. Tuna comes in handy cans than be ripped open. Some even comes in airtight packet so that you can carry it around.
Muscle Building Foods 5
Do not forget about milk and soy! This stuff is good stuff. Although they may appear as liquid, they are a good source of protein and when taken with meat, they compliment the amino acids supplied by the meat. 100 grams of tofu made from soy contains 8 grams of protein. One glass of low fat milk contains roughly 8 grams of protein. You have to be careful not to over do the milk because milk does contain lots of fat. Choose the low fat or the pasteurized version.
There you go, five choices of muscle building foods to fill up your menu. Make sure you include protein in all your meals, spread them out evenly in a day. Try to shot for 2.0 to 2.6 grams of protein per kilogram of body weight for positive nitrogen balance. This will give you optimum results along with intense weight training.
Apr 02, 2016 • By Jonthan Wilder •
Hemorrhoids are caused by the pillow like cluster of veins that are found below the mucus membrane in the inner lining of the lowest part of the excretory system. The problem starts if the veins get swollen to battle the gravity and push blood towards heart. The most common solution to the problem is use of rubber band to push back hemorrhoids and it doesn't guarantee non-reoccurrence of the condition. The imbalance in the metabolic function along with changes in endocrine system makes it very difficult for old people to counter this kind of painful condition. Herbal remedies to treat bleeding hemorrhoids can get rid of the problem and even prevent its reoccurrence.
Human body has a sensitive digestive and excretory system suffers from damage over ages of improper use. Many suffer from the problem of hemorrhoids, internal or external, by the middle age and in old age. More than 10 percent of US adult population suffers from the problem of hemorrhoids that is believed to be a common aging side effect. The most common reason for a number of health issues is the improper functioning of the digestive system and the excretory system. Ayurvedic cures contain a mixture of extracts collected from medicinal plants that can help in preventing the causes of hemorrhoids by improving bowel health and reducing the problem of infections to the intestine. Herbal remedies to treat bleeding hemorrhoids as provided by Pilesgon capsules contains the extracts from Sapindus Mukorossi, Mesua Ferrea, Acacia Catechu, Vernonia Anthelmintica, Berberis, Bryophyllum Calycinum etc. The extract improves liver functioning and increases the capability of bowel to hold moisture.
Sapindus Mukorossi is used to cure piles as it contains important phyto-chemicals which can reduce extensive cellular damage and has hepato-protective effect on body. The plant species is used for the treatment of tooth disorders, piles, asthma, and its fruits are valued for saponins.
Mesua Ferrea contains phyto-chemicals that show potent antioxidant activities againstbacterial infections. It improves liver functioning and protects against aging related damage to the metabolic system.
Herbal remedies to treat bleeding hemorrhoids contain the herb Acacia Catechu that was traditionally taken empty stomach with lemon juice to cure piles. The herb is believed to be anti-inflammatory and tissue protecting in nature. If taken internally it works as anti-diarrheal and analgesic. In human studies, the herb showed the anti-inflammatory effects onosteoarthritis patients. It is a rich source of gallic acid derivatives e.g. catechin, epicatechin etc.
Vernonia Anthelmintica was taken traditionally to get rid of intestinal infections, parasites and reduce pain and inflammation in the abdomen. A study on mice showed the fruits of the plant possess central and peripheral analgesic activities. The extract of fruits also has acute and chronic anti-inflammatory effects on laboratory rats. The tannins, saponins, steroids and flavonoids of the fruits are responsible for these properties.
Herbal remedies to treat bleeding hemorrhoids contain a number of herbs that can reduce inflammation and pains caused by internal and external hemorrhoids, and revive the power of damaged tissues in the lowest part of intestine by improving blood flow to the intestinal tissues.