Benfotiamine (S-benzoylthiamine monophosphate) is a compound that is an analog vitamin B1 (thiamine). Because it is lipid-soluble, the body metabolizes benfotiamine more quickly than vitamin B1. Upon dephosphorylation of benfotiamine in the intestinal  tract, a lipophilic molecule is produced which readily diffuses across cell membranes and is absorbed much better than water soluble thiamine salts. This attribute allows for more absorption in the intestines and in target tissues as compared with thiamine itself. Higher plasma thiamine levels are achieved with oral benfotiamine intake, and blood and tissue concentrations are maintained long time. Oral benfotiamine dosages in these experiments ranged from 40-250 mg daily.

1954, Fujiwara discovered a group of lipid-soluble thiamine derivatives, subsequently called allithiamines because they occur naturally in Allium family vegetable: roasted crushed garlic, onions, leeks. Benfotiamine has been existing in Japan since 1961 and is sold under the trade name “Biotamin“. Has been marketed in Germany since 1978 as under the trade name “Milgamma Mono“. Used for decades in Europe as a prescription drug, benfotiamine reduces the progression of diabetic nerve, retinal, and kidney, damage, and relieves the painful symptoms of diabetic neuropathy. Various clinical trials have demonstrated a reversal in diabetic neuropathy, with improved nerve function and alleviation of pain.

Benfotiamine Benefits

Benfotiamine activates transketolase efficiency, therefore facilitating conversion of harmful glucose metabolites and affecting Advanced Glycation End product (AGE) formation. Advanced glycation end products are caused by hyperglycemia, a trouble that diabetics often have. Different researchs have shown that benfotiamine inhibits 3 important pathways that lead to the formation of toxic substances such as advanced glycation end products. In a clinical trial with 6 patients, benfotiamine lowered Advanced Glycation End Product (AGE) by 40 percent.

Lab experiments and controlled trials have confirmed that benfotiamine alleviates and may even reverse diabetic neuropathy, kidney disease, endothelial dysfunction, peripheral vascular disease, and diabetic retinopathy.

Benfotiamine is remarkably active at inhibiting the formation of AGE (Advanced Glycation End products). It increases threefold the concentration of the endogenous enzyme transketolase which breaks down AGE and converts them into inoffensive compounds. AGE’s main targets are the nerves, eyes, blood vessels and kidneys, and since diabetics produce AGE in excess. In a study, benfotiamine effectively increased transketolase activity in cell cultures by an dramatically 300 percent, compared to a mere 20 percent for thiamine.

In an in vitro study of human endothelial progenitor cells, scientists demonstrated that benfotiamine can help correct hyperglycemic impairment of EPC differentiation into mature, healthy endothelial cells. In 2006, experts at the ‘American Diabetes Association‘ found benfotiamine to be useful in preventing blood vessel degeneration in people with type 2 diabetes.

A double-blind study in Germany found that diabetes patients with polyneuropathy who supplemented with 100 mg of benfotiamine four times daily for 3 weeks demonstrated statistically remarkable development in nerve function scores. A study reported in Experimental and Clinical Endocrinology and Diabetes in November 2008 examined the feature of benfotiamine on individuals with diabetic-neuropathy. 2 groups received the benfotiamine, first group taking 300 mg per day, while the other group took 600 mg. Found those individuals in the 600 mg group  the most development in they neuropathy. 13 patients with type 2 diabetes were given a three-day trial of benfotiamine and challenged with a hyperglycemic diet. The researchers concluded that benfotiamine had important prevented both macrovascular and microvascular endothelial dysfunction and oxidative stress in these subjects challenged with a meal rich in advanced glycation end products ages.

Foods Contain Benfotiamine

Benfotiamine is found naturally in onions, garlic, shallots, leeks, and other members of the allium family of vegetables.

Dosage

Benfotiamine is well tolerated at doses up to 600 mg daily or higher. Based on clinical trials to date, daily doses of benfotiamine range from 300-450 milligrams  daily in divided doses. Animal-based studies in which high doses of up to 100 milligrams benfotiamine/kg bw for six months were administered, reported no negative effects.

L-Theanine (delta-glutamylethylamide) is an amino acid found in green tea. Was first isolated in the 1940s. This amino acid, is able to cross the blood-brain barrier and is considered to be psychoactive. Possesses neuroprotective, mood-enhancing, and relaxation properties. Theanine appears to have a role in the formation of the inhibitory neurotransmitter Gamma Amino Butyric Acid.

Klonopin, Valium, and Ativan are  commonly prescribed anti-anxiety medicaments. But, long term use of this class of drugs named benzodiazepines, can lead to physical and psychological dependence, and like all drugs, they have the risk to damage the liver with extended use. Clinical findings show that l-theanine may help reduce stress and promote relaxation.

L-Theanine for Anxiety and Depression

Research on human volunteers has demonstrated that theanine creates a sense of relaxation approximately 30 minutes after ingestion by two different mechanisms. 1-Theanine directly stimulates the production of alpha brain waves, creating a state of deep relaxation and mental alertness similar to what is achieved through meditation.2- Theanine is involved in the formation of the inhibitory neurotransmitter, gamma aminobutyric acid (GABA). Gamma-aminobutyric acid is an important neurotransmitter that is abundant and widely distributed throughout the central nervous system. Low  levels or decreased GABA function in the brain is associated with different neurological and psychiatric problems, but most primarily depression, anxiety, insomnia and epilepsy. According to a 2006 info in the “Journal of Herbal Pharmacotherapy“, L-theanine not only increases GABA levels in the brain, it also increases serotonin and dopamine levels. Theanine may alleviate anxiety by inhibiting the barrage of brain excitation associated with anxiety states, according to a study reported in the January 2007 Biological Psychology journal.

The human brain generates various types of weak electric pulses that are classified as alpha, beta, delta and theta waves. Each of these waves are associated with particular physiological activity e.g. theta waves are associated with drowsiness while alpha waves are associated with relaxation. Clinical studies have shown that L-theanine powerfully activates alpha waves and induces relaxation in test subjects. A study reported in Trends in Food Science and Tech found electroencephalographic evidence on how l-theanine affects the brain. L-Theanine increases the alpha brain frequency which means relaxes the mind without causing drowsiness. A study reported in 2008 in “Asia Pacific Journal of Clinical Nutrition” found that 50 mg of l-theanine significantly increases alpha brain wave activity within 40 to 90 min of ingestion.

L-Theanine Dosage for Anxiety

L-theanine supplements are taken in doses ranging from 200 mg to 800 mg per day. In a monograph reported by Alternative Medicine Reviews in 2010, the recommends taking 200 mg twice or three times daily to treat anxiety. (The approximate 1 cup of green tea is estimated to contain 20 mg of L-theanine). Though there are no reported side effects, the Food and Drug Administration (FDA) recommends that people do not take more than 1,200 mg daily. Suntheanine®, a pure form of L-Theanine, is a patented supplement and a registered trademark of Taiyo International.

GABA (Gamma-aminobutyric acid) is a naturally occurring amino acid that your body produces under normal circumstances. It is the most widespread inhibitory neurotransmitter of the brain and helps in maintaining a proper balance between the mind and the body. Neurotransmitters are chemical molecules that brain cells and nerve cells use to communicate with each other. GABA is found in almost every region of brain, and is formed through the activity of the enzyme glutamic acid decarboxylase. Drugs in the benzodiazepine-receptor-agonist family exert their effect by facilitating the ability of GABA to bind to receptor sites in the brain.

GABA Deficiency

In the brain, GABA insufficiency is believed to cause rapid firing of nerve cells leading to increases in agitation, anxiety, panic attacks, headaches, Parkinson’s disease and thought disorders. Because the chemical is a component of the body’s neurological system, deficiencies have also been linked to a number of neurological conditions, including seizures and fibromyalgia. GABA analog gabapentin has been approved in the United States for the treatment of epileptic seizures and postherpetic neuralgia.

GABA Benefits

Gamma-aminobutyric acid is an important neurotransmitter that is abundant and widely distributed throughout the central nervous system. It is produced by the body from glutamate, although this process becomes less efficient with age. Low  levels or decreased Gamma-aminobutyric acid function in the brain is associated with different neurological and psychiatric problems, but most primarily depression, anxiety, insomnia and epilepsy. A study reported in the journal “Biological Psychiatry” in 2010 indicates that individuals with major depression may be more likely to have low levels of Gamma-aminobutyric acid. British scientists have found that the age-related decline in higher brain functions is due, in large part, to a lack of the inhibitory neurotransmitter, Gamma-aminobutyric acid.

Some anti-anxiety drugs like benzodiazepines and barbiturates generally work by increasing the amount of GABA in the synapses that is available to bond to GABA receptor sites. While many individuals diagnosed with anxiety take prescription medications such as Xanax, Valium or Ativan, benzodiazepine drugs that stimulate GABA receptors, these drugs often produce negative effects.

Gamma-aminobutyric acid is named to as the ‘brain’s natural calming agent, and by inhibiting over-stimulation of the brain, GABA may help promote relaxation and ease nervous tension. Initial studies in the 1950s suggested that GABA had a relaxing effect on the brain and could be useful in the therapy of anxiety and schizophrenia. Gamma-aminobutyric acid may help to lower the effects of stress via its calming role by attaching to the benzodiazepine receptors in your brain. GABA hinders the transmission of nerve impulses from one neuron to other. It has a quieting or calming  influence. Unlike benzodiazepines like Xanax and Valium that are created to enhance the effects of GABA in your brain, GABA provides the same relaxing anti anxiety without the addictive side effects.

GABA stimulates the anterior pituitary gland to secrete higher levels of HGH (human growth hormone). The researchers of study reported in “Medicine and Science in Sports and Exercise” in 2008 found that oral GABA supplements elevated growth hormone levels.

GABA Dosage for Anxiety

Clinical studies show that doses of 800 mg a day are effective for insomnia and anxiety. Some physicians prescribe GABA in doses of up to 200 milligrams, 4 times a day, for a maximum daily dose of 800 milligrams.

GABA Side Effects

GABA may produce excessive drowsiness when taken with other drugs that have a tranquilizing property, including codeine and other narcotic pain relievers, sedatives, antidepressants, and muscle relaxants. Always let your physician know if you are taking GABA or other supplements. Maximum safe doses in young children, pregnant or nursing women, or individuals with severe  kidney or liver illness have not been established.

Natural GABA Enhancers

• GABA is formed through the activity of the enzyme glutamic acid decarboxylase (GAD). GAD requires vitamin B6 as a cofactor, which can be used to regulate the levels of GABA. Also works in synergy with nutrients such as inositol and niacine to reduce symptoms of stress and anxiety. The tolerable upper intake level of vitamin B6 (Pyridoxine) for adults is 100 mg per day, according to the Linus Pauling Institute.

• L-theanine is a naturally occurring amino acid found in the primary component in green tea. This amino acid primarily affects dopamine, serotonin, and especially GABA levels. By increasing the levels of GABA in the brain, theanine is considered  to produce calming effects. According to a 2006 info in the “Journal of Herbal Pharmacotherapy“, L-theanine not only increases GABA levels in the brain, it also increases serotonin and dopamine levels. L-theanine supplements are taken in doses ranging from 200 milligrams to 800 milligrams per day. (Suntheanine® is the patented form of L-theanine and the trademark of  Taiyo International, the firm that originally isolated the amino acid into an effective supplement for consumers).  L-Theanine Dosage For Anxiety

• Valerian Root comes from the Valeriana officinalis plant. Has a long history of use as a tranquilizer by increasing the effect of GABA on its receptors. Scientists, they believe it increases the amount of a chemical called GABA in the brain. GABA helps regulate nerve cells and has a calming property on anxiety. Valerian root extract is given in supplement form in doses of 100 to 600 milligrams before or after stress related events.

• Magnesium Glycinate is a soluble form of magnesium. Deficiency in magnesium may lead to anxiety-related behavior, according to a 2004 study reported in “Neuropharmacology“. Work up to a daily dose of 400 to 1,000 mg. provides a highly natural approach when paired with vitamin B-6 (Pyridoxine).

• Kava Kava is a shrub belonging to the pepper family, Piperaceae. The kavalactones found in kava kava appear to alter levels of the neurotransmitters serotonin and dopamine in your brain, which are 2 chemicals that promote a happy mood and feelings of pleasure. The lactones contained in kava kava may also stimulate the production of more attachment sites in the body for a different neurotransmitter, GABA. A study reported in the November 2003 of Phytomedicine found that 73 % of patients treated with kava kava extract over 4 weeks experienced decreased anxiety. The German Commission E (an official government agency similar to the  FDA), recommends taking a kava supplement that supplies 60 mg to 120 mg of kavalactones daily for no longer than three months at a time. (Look for standardized kava root extract in tablet or liquid form that contains 30 to 70 % kavalactones, the active ingredient in kava root)

• Taurine is a non-essential amino acid produced by the body through the synthesis of 2 other amino acids, cysteine and methionine. Taurine increases the effectiveness of GABA. Typical doses of 1,000 to 5,000 milligrams per day have been used safely.

Milk thistle (Silybum marianum), is a spiny plant native to the Mediterranean. Silymarin is the name of the active component extracted from milk thistle seeds. The active substance in milk thistle, silymarin, is a mixture of flavonolignans, primarily consisting of four isomers; silybin, isosilybin, silychristin, and silydianin. Most supplements are standardized according to their silybin content. Other constituents; quercetin, taxifolin, dihydrokaempferol, kaempferol, apigenin, naringin, eriodictyol, chrysoeriol, palmitic acid, linoleic acid.

Silymarin Benefits

Milk Thistle (silymarin) has been the subject of more than 300 clinical and lab trials. Cirrhosis, fatty liver, liver poisoning alcoholic and viral hepatitis are found to affect positively to milk thistle extracts. A lab study showed that silymarin may increase glutathione content in the liver and intestines by up to 50 %.  Silymarin  increases the activity of SOD in red blood cells (erythrocytes) and white blood cells (lymphocytes) formed in the lymphatic tissue in patients with liver disease. Intravenous silymarin is a life-saving emergency room treatment used throughout Europe in cases of poisoning.

Silymarin is an natural remedy recognized in Germany as a therapy for liver problems. In 1968, German scientists discovered the active flavonoid complex silymarin, which provides milk thistle therapeutic effects. The German Commission E  (an official government agency similar to the US FDA) approved the use of silymarin as a treatment for toxic liver disease and a supportive treatment for chronic inflammatory liver illness and cirrhosis of the liver. Silymarin  may protect the liver from toxic chemicals and have been tested for their potential to make chemotherapy more effective or less toxic as well as to slow or stop the growth of cancer cells.

Milk thistle inhibits the factors responsible for liver damage and stimulates the growth of new liver cells to replace damaged ones. Neutralizes liver cell damage caused by toxins and strengthens the liver cells’ outer membranes to prevent future harm. Stimulates protein synthesis in liver cells by increasing RNA and DNA activity, enhancing the regeneration of liver cells. Milk thistle has been shown to increase the glutathione content of the liver. Specifically, silymarin has been shown to stimulate the glutathione S-transferase pathway and alter the intracellular concentration of glutathione. Glutathione is a metabolic enzyme that works as antioxidant and reduces the effect of some toxic substance.  (For more information Glutathione Foods )

Hepatitis

In the 1970’s, two German research group proved through clinical studies that 70 percent of people suffering from chronic liver diseases had a vastly improved chance of recovery when given between 210 – 420 milligrams of silymarin daily over periods ranging from 6 weeks to 2 years. Milk thistle found to affect liver functioning, according to an writing reported in November 2000 in the journal Drug Metabolism and Disposition.   A 2010 Hepatology experiment proved that milk thistle inhibited hepatitis C infection by interfering with viral transmission and viral entry into liver cells.

In a 6-month double-blind study of 36 patients with chronic alcoholic liver illness, the group given silymarin (Legalon) showed normalization of their bilirubin, aspartate transaminase and alanine transaminase serum levels. In different study, 106 patients with mild acute and subacute liver illness characterized by elevated serum transaminase levels were randomized to receive silymarin or placebo. Of the 97 patients who completed the 4-week study, there was a statistically considerable greater decrease in transaminase levels in the silymarin group.

A clinical trial of 16 patients who didn’t respond to ribavirin and interferon therapy, silymarin important reduced the viral load of hepatitis C.  In 7 of the patient  the virus decreased to undetectable levels after 14 days of treatment. The findings of the study, reported in the March 30, 2010 issue of the Proceedings of the National Academy of Sciences of the USA, show that silymarin inhibit the development of the hepatitis virus by way of their anti-inflammatory and antioxidant effects. In a far-reaching analysis of for liver diseases reported in Pharmaceutical Biology in May 2011, concluded that milk thistle is effective in protecting the liver from damage caused by hepatitis, cirrhosis and other liver ailments.

Cirrhosis

Some studies indicate silymarin slows the progression of cirrhosis. In a comment of previous clincial studies with human subjects, reported in the  Forschung Komplementmedicine in 2008, the writers concluded that milk thistle is a positive option as a general supportive supplement for the liver and in treatment of cirrhosis.

Liver Damage

Liver-damage, can occur from a number of toxins, including alcohol and drugs such as acetaminophen. A 1998 study found that silymarin may protect the liver from toxicity from taking acetaminophen, phenothiazines and dilantin. Acetaminophen (Tylenol) overdose is the leading cause of acute liver failure in the world. Using acetaminophen with alcohol increases the likelihood of toxicity. Milk thistle (silymarin) enters the liver cells and prevents those cells from absorbing toxins.

Amanita Phalloides Mushroom Poisoning

From of old, milk thistle was used as an antidote for death cap mushroom poisoning. The Amanita phalloides mushroom, named the “death cap,” produces severe nausea, vomiting, and watery diarrhea within 5 to 12 hours of ingestion. A antidote for poisoning by the Amanita phalloides, silymarin prevents the mushrooms toxins from circulating throughout the body. Studies animal-based  have shown that silymarin not only reduces the risk of death if administered within 24 hours, yet all signs of toxicity disappear if given within ten minutes. Silymarin inhibits the binding of the toxins in the mushroom to hepatocytes and interrupts the enterohepatic circulation of the toxins. In a group of 49 patients with Amanita phalloides poisoning, physicians rated the results “spectacular” and  “amazing” after patients were given injections (20 mg/kg daily) of silybin. All of the patients survived, even though they were treated 24 to 36 hours after poisoning, when liver damage had already occurred. The death rate in emergency rooms from Amanita phalloides mushroom poisoning is usually 30 to 40 %.

Anti-Proliferate Property

Silymarin and  silybin exert anti-proliferate property by potentially stopping the growth of cancer cells. Has shown to protect against liver cancer by decreasing the activity of carcinogenic and toxic chemicals as reactive oxygen species. Studies by the “Columbia University Medical Center” indicate that silymarin may limit liver inflammation and damage caused by chemotherapy for cancer. In addition, silymarin was shown to reduce liver toxicity associated with chemotherapy in children with acute lymphoblastic leukemia and cisplatin-induced nephrotoxicity  .

Silymarin Dosage

Milk thistle supplements, are standardized to a concentration of 70-80 percent of flavone lignans including isosilybinin, silybinin, silydianin and silychristin, which are collectively called silymarin. A typical daily dose ranges from 140 to 420 mg of silymarin, usually divided into 2 or 3 doses. Most clinical trials have used daily doses of 420 to 480 mg silymarin, divided into 2 or 3 doses daily. After oral usage, milk thistle is absorbed from the gastrointestinal tract with a bioavailability of approximately 23-47%. Various studies show that a phosphatidylcholine-silymarin complex may be absorbed more easily than regular standardized milk thistle. The silymarin-phosphatidylcholine complex should be taken in doses of 100 to 250 mg two times per day. In Europe, the active compound silymarin is given by intravenous infusion as the only effective antidote for A. phalloides.