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SAMe with Cofactors

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“SAMe with Cofactors” is a special blend that includes the major nutrients required for S-adenosyl methionine, known as SAMe, to be activated and effective, in an unusually pure formulation. SAMe is a very unstable compound that is highly hygroscopic, meaning that it absorbs moisture from the air which could denature it. Many SAMe supplements attempt to keep SAMe stable in coated tablets that include shellacs, waxes, and plastics containing phthalates, which are known endocrine disruptors. This formula combines SAMe with calcium and magnesium in a way designed by the Italian nutraceutical specialists Gnosis S.p.A. in Milan that keeps it very shelf-stable at room temperature without unhealthy additives. Furthermore, “SAMe with Cofactors” provides the necessary amounts of vitamin B12 and folic acid in the right proportions for SAMe to work. These cofactors are required with SAMe for the methylation functions and sulfur-reactions that bring mood, nervous system, joint and liver benefits. This formula also includes vitamin B6 to ensure that SAMe is efficiently cleared and to prevent homocysteine elevations. Our patients have reported notable and ongoing improvements in osteoarthritis pain on “SAMe with Cofactors”, sometimes noticing relief within hours of a dose, and they report increasing relief over months or years. We have seen very good benefits for mood and liver function panels in our clinic.

About SAMe with vitamins B6 and B12, and folic acid

S-adenosyl-methionine, or SAMe, naturally forms in the body from the essential amino acid methionine and adenosine triphosphate (ATP), an energy-releasing molecule. SAMe is involved in dozens of metabolic reactions, including brain neurotransmitter activity and cartilage formation, but our intrinsic levels can be insufficient. SAMe has been used in the US since 1999, but it has been a prescription drug in Italy for depression since 1979, in Spain since 1985, and in Germany since 1989. Its value for osteoarthritis was discovered by accident when patients in depression trials reported unexpected joint improvements. SAMe is the major methyl donor in the body: it functions closely with folic acid and vitamin B12 in methylation reactions, where a small methyl hydrogen-carbon group is transferred to another molecule. Methylation is critical in formation of brain chemicals and detoxification. SAMe is also necessary for the body to make sulfur-rich compounds including cartilage elements like chondroitin and the powerful antioxidant glutathione.

For depression and seasonal affective disorder, SAMe facilitates methylation which is critical for the brain's manufacture of monoamines, neurotransmitters including serotonin and dopamine, and phosphatidylserine. SAMe also enhances the ability of serotonin and dopamine to bind well to their receptors. A number of neurotransmitters, fatty acids, phospholipids, and other chemicals must accept methyl groups from SAMe to become active. Usually the brain can produce all the SAMe it needs, but depressed patients cannot make enough of their own, and their methylation functions are often lacking. Both serum and cerebrospinal fluid levels of SAMe have been found to be low in depressed patients. Taking supplemental SAMe leads to better serum levels of serotonin and dopamine, which bind more effectively to their receptors, boosting mood. SAMe is one of the most effective natural antidepressants: numerous studies show that it can be as effective as certain prescription antidepressants, giving a 50% better score on the Hamilton Depression Rating Scale and other measures of mood than some standard drugs, and SAMe can have a faster onset of action. SAMe increases metabolites of serotonin and dopamine in the cerebrospinal fluid; membranes are kept more fluid and neurotransmitter receptors become more responsive. SAMe is also valuable for premenstrual syndrome and for a more severe form of PMS involving deep mood swings called premenstrual dysphoric disorder (PMDD). Vitamins B6, B12 and folic acid also play important roles in mood support and the brain's ability to make its uplifting neurotransmitters. These nutrients work in collaboration with SAMe, and we see the best results when they are taken in combination. EEG studies show positive antidepressant changes with SAMe: an increase in power in the alpha-2 and beta frequencies, and an acceleration of the alpha, an increase in absolute delta and a decrease in absolute alpha power, an increase in relative delta and a decrease in relative alpha power, a slowing of the delta/theta centroid. SAMe worked better than placebo. These EEG findings are typical of active antidepressants. SAMe boosts brain phosphocreatine, and lowers adenosine triphosphate levels in the brain. This is consistent with SAMe being involved in the production of creatine, which in turn forms phosphocreatine, suggesting that SAMe positively alters cerebral bio-energetic status.

For osteoarthritis, SAMe is a potent remedy that can increase cartilage on scans. It is made in the body, but is often low in people with degenerative joint disease. A deficiency of SAMe can lead to loss of the gel-like consistency and shock-absorbing ability of cartilage, accelerating osteoarthritis. Extensive research shows impressive improvements of pain, stiffness, and range of motion with SAMe. MRI scans have shown that SAMe leads to increased cartilage formation, especially for osteoarthritis of the hands, meaning that SAMe actually helps to reverse joint damage and to rebuild healthy structure and function. SAMe is required in the body for formation of sulfur-continuing components in cartilage; some is made in our tissues from the essential amino-acid methionine. Over time, more than twenty thousand patients with degenerative joint disease have participated in numerous clinical trials with SAMe. Compared to ibuprofen, people with osteoarthritis of the knee, hip or spine taking SAMe had as much or more reduction of morning stiffness, pain at rest or in motion, crepitus (crackling joint sounds), swelling and mobility. Several studies have found that patients taking SAMe received as much improvement of pain, circumference of joints and walking time as those on naproxen or placebo, after six weeks or more. Other research has shown SAMe to be as effective as indomethacin or piroxicam, but without the stomach side-effects. Over another two-year trial, SAMe brought relief within weeks for osteoarthritis of the neck, low back, knee and hip, and improvements continued for 24 months. The use of high doses of SAMe up to 1,200mg. daily, in a large study with several thousand patients, brought striking benefits for up to 92% with arthritis of the hands, hips and knees. Biochemically, SAMe works closely with vitamin B12 and folic acid as a methyl-donor: In human cartilage cells, called chondrocytes, it may increase the synthesis and release of the cartilage element proteoglycan especially for osteoarthritis patients. SAMe has been shown to have anti-inflammatory and analgesic properties, though the mechanism of this effect is unclear. It does not seem to be mediated via the prostaglandin system, or via changes in fatty acid balance. High oral doses for thirty days or more do not affect the integrity of the gastric mucosa, which suggests that SAMe does not interfere with the cyto-protective function of prostaglandins in gastrointestinal tissues. SAMe is most effective for arthritis when taken in combination with vitamins B6, B12 and folic acid.

SAMe protects the liver from damage, it enhances healthy bile flow, and improves liver function. It may help the liver via several mechanisms. Glutathione, the major antioxidant in the liver, plays a key role in detoxification and limiting oxidative damage, and SAMe is critical for hepatic glutathione synthesis. Research confirms that SAMe helps liver injury to heal and helps liver disease because it boosts glutathione, for chronic liver disorders and alcoholic liver disease patients. Clinical trials indicate that SAMe may decrease fatty deposition in the liver, and protect against alcohol damage. SAMe enhances methyl transfer, essential to a healthy phospholipid bilayer in membranes of normal cells and important for membrane fluidity. Studies also show that SAMe can detoxify bile acids to reduce their ability to cause liver cell injury, and protect against ethanol damage to the liver. SAMe improves bile flow via its beneficial effects on membrane fluidity and the activity of the Na+K+ ATPase-dependent pump, and by adding more sulfur to bile salts so they are more soluble. This relieves cholestasis (bile stagnation). SAMe helps to methylate the oral contraceptive chemical ethinyl estradiol and prevent the bile stagnation it can cause. Hormones, including estrogen, contribute to cholestasis of pregnancy with which SAMe may help. SAMe can repair the glutathione transport system inside mitochondria, protect liver cells from the toxic effects of cytokines, and increase helpful methylation of DNA. The results of these cellular actions include helping Gilbert's syndrome, where bilirubin is chronically high causing poor appetite and malaise. SAMe can reduce bilirubin levels and symptoms. It also reduces the risk of developing liver cancer for patients with cirrhosis and chronic hepatitis.

SAMe appears to lower homocysteine by helping the body metabolize it. Homocysteine is a toxic amino acid, a breakdown product of protein metabolism, which if elevated is a risk factor for cardiovascular and kidney disease. Although SAMe is eventually converted in the body to homocysteine, a study at McLean Hospital in MA found that even 1600mg. daily of SAMe for four weeks did not increase homocysteine. Apart from SAMe, vitamins B6, B12 and folic acid are all beneficial to promote clearance of homocysteine.


1 capsule provides: SAMe, S-Adenosyl Methionine 200mg, Vitamin B6 (as Pyridoxal 5' Phosphate) 2mg, Vitamin B12 (as methylcobalamin) 500mcg, Folate (as 5-methylfolate) 200mcg, Calcium (citrate, malate) 75mg, Magnesium (citrate) 75mg.

Other Ingredients: vegetarian cellulose capsule, L-leucine.

Free of: - This product does Not contain: artificial coloring, artificial flavoring, preservatives, parabens, gluten, corn, ingredients of animal origin, shellfish, egg, salt, sugar, soy, wheat, yeast


Always take natural remedies under the supervision of your health care provider. Do not use ‘SAMe with Cofactors' without consulting your physician if you take medications that lower blood sugar including metformin or insulin, as SAMe may lower blood sugar levels and medication adjustments may be necessary. Monitor blood sugar levels if you use natural remedies to lower blood glucose including chromium, gymnema, cinnulin, or banaba. SAMe may lower blood pressure: if you have hypertension or take medication for high blood pressure such as hydrochlorothiazide, losartan, Lisinopril, spironolactone or diltiazem then monitor your blood pressure carefully. Do not use ‘SAMe with Cofactors' without the advice of your healthcare professional if you take blood thinners including warfarin, heparin, antiplatelet drugs such as clopidogrel (Plavix), or nonsteroidal anti-inflammatory drugs such as ibuprofen or naproxen or aspirin, as SAMe may enhance their actions and affect bleeding risk. Avoid taking SAMe if you also use agents that treat psychiatric disorders, alcohol, antidepressants including MAOIs or SSRIs, levodopa, or tricyclic antidepressant drugs. Avoid SAMe if you have an anxiety disorders, depression, or bipolar disorder: because SAMe has antidepressant activity it could exacerbate the manic phase. ‘SAMe with Cofactors' may possibly be safe for less than four weeks during the third trimester of pregnancy, when it is sometimes used for cholestasis, but do not take it without the guidance of your physician, as there is insufficient data on safety during pregnancy or breastfeeding.


Metabolic Maintenance
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60 capsules

Benefits of Consistency

“With the right vitamins, herbs and foods, your health can continue to improve over time, as vibrant new tissues replace old cells. Our patients often feel increasing vitality as medical tests get better and better, year after year.”

- Dr. Rachelle Herdman

Dr. Herdman is a graduate or member of the following organizations:

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