SAMe Supplementation
Posting this forum to discuss the benefits and detriments of s-adenosyl-l-methionine supplementation.
Starting with a good article on this website: A Supplement for the 21st Century
"Recently a great deal of media attention has focused on the supplement SAMe, or s-adenosyl-l-methionine. Clinical trials in Europe and the United States have shown that SAMe can be beneficial in modifying brain function, making it a useful supplement for treating depression. SAMe is also shown beneficial in treating degenerative joint disease and liver problems."
The article references these first hand sources:
Depression:
Baldessarini RJ, Neuropharmacology of S-adenosyl-L-methionine. Am J Med 83 (Suppl. 5A), 95-103, 1987
Reynolds E, Carney M, and 2. Toone B, Methylation and mood. Lancet ii, 196-199, 1983.
Bottiglieri T, Laundry M, Martin R, et al., S-adenosylmethionine influences monoamine metabolism. Lancet ii, 224, 1984.
Janicak PG, et al., Parenteral S-adenosylmethionine in depression: A literature review and preliminary report. Psychopharmacology Bulletin 25, 238-241, 1989.
Bell, K.M. ,et al S-adenosylmethionine treatment of depression: A clinical trial. Am J Psychiatry 1988,145:110-14
De Vanna M and Rigamonti R, Oral S-adenosyl-L-methionine in depression. Curr Ther Res 52, 478-485, 1992.
Carney MWP, Toone BK, and Reynolds EH, S-adenosylmethionine and affective disorder. Am J Med 83 Suppl. 5A), 104-106, 1987.
Salmaggi P, et al., Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychother Psychosom 59, 34-40, 1993.
Kagan FL, et al. Oral S-adenosylmethionine in depression: A randomized, double-blind placebo-controlled trial. Am J Psychiatry 147, 591-595, 1990.
Russo A, et al., Efficacy of S-adenosyl-L-methionine in relieving psychological distress associated with detoxification in opiate abusers. Curr Ther Res 55, 905-013, 1994.
Arthritis:
Solomon L, Drug induced arthropathy and necrosis of the femoral head. J Bone Joint Surg 55B, 246-251, 1973.
Konig H, et al., Magnetic resonance tomography of finger polyarthritis: Morphology and cartilage signals after ademethionine therapy. Aktuelle Radiol 5, 36-40, 1995.
Glorioso S, et al., Double-blind multicenter study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 5, 39-49, 1985.
Marcolongo R, et al., Double-blind multicentre study of the activity of S-adenosyl-methionine in hip and knee osteoarthritis. Curr Ther Res 37, 82-94, 1985.
Domljan Z, et al., A double-blind trial of ademethionine vs naproxen in activated gonarthrosis. Int J. Clin Pharmacol Ther Toxicol 27, 329-333, 1989.
Muller-Fassbender H, Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med 83 (Suppl. 5A), 81-83, 1987
Berger R and Nowak H, A new medical approach to the treatment of osteoarthritis: Report of an open phase IV study with ademethionine (Gumbaral). Am J Med 83 (Suppl. 5A), 84-88, 1987.
Fibromyalgia:
Jacobsen S, et al., Oral S-adenosylmethionine in primary fibromyalgia: Double-blind clinical evaluation. Scand J Rheumatol 20, 294-302, 1991.
Tavoni A, et al., Evaluation of S-adenosylmethionine in primary fibromyalgia: A double-blind crossover study. Am J Med 83 (Suppl. 5A), 107-110, 1987.
Pascale RM, et al., Chemoprevention of rat liver carcinogenesis by S-adenosyl-L-methionine: A long-term study. Cancer Res 52, 4979-4986, 1992. Scandinavian J. of (Gastroenterology 24, 407, 1989.)
Liver:
Mazzanti R, et al., On the antisteatosic effects of S-adenosyl-L-methionine in various chronic liver diseases: A multicenter study. Curr Ther Res 25, 25-32, 1979.
Frezza M, et al., Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis: A double-blind, placebo-controlled study. Gastroenterology 99, 211-215, 1990.
Di Benedetto P, Iona LG and Zidarich V, Clinical evaluation of S-adenosyl-L-methionine versus transcutaneous nerve stimulation in primary fibromyalgia. Curr Ther Res 53, 222-229, 1993.
Total glutathione before and after 6 months treatment with 1,200 mg oral SAMe. (Scand. J. Gastroent 24:407, 1989)
Bombarbieri G, Milani A, Bernardi L and Rossi L, Effects of S-adenosyl-L-methionine (SAMe) in the treatment of Gilbert’s syndrome. Curr Ther Res 37, 580-585, 1985.
Angelico M, et al., Oral S-adenosyl-L-methionine (SAMe) administration enhances bile salt conjugation with taurine in patients with liver cirrhosis. Scand J Clin Lab Invest 54, 459-464, 1994.
Vitamin B supplements
Water extracted Kava effective in reducing anxiety
I'm posting this here mainly because this medicinal remedy addresses one of the main reasons for SAMe supplementation - to address anxiety and depression.
I find it an interesting coincidence that both SAMe and Kava have an impact on the liver in particular. I'm unaware of how Kava affects seratonin production, but I'd be curious to know.
Medicinal Plant Kava Safe And Effective In Reducing Anxiety, Study Suggests
ScienceDaily (May 14, 2009) — Researchers at the University of Queensland in Australia have found a traditional extract of Kava, a medicinal plant from the South Pacific, to be safe and effective in reducing anxiety.
In 2002 Kava was banned in Europe, UK and Canada due to concerns over liver toxicity.
“When extracted in the appropriate way, Kava may pose less or no potential liver problems. I hope the results will encourage governments to reconsider the ban,” Mr. Sarris said.
“Ethanol and acetone extracts, which sometimes use the incorrect parts of the Kava, were being sold in Europe. That is not the traditional way of prescribing Kava in the Pacific Islands. Our study used a water-soluble extract from the peeled rootstock of a medicinal cultivar of the plant, which is approved by the Therapeutic Goods Administration of Australia and is currently legal in Australia for medicinal use.”
Journal reference:
1. Sarris et al. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum
. Psychopharmacology, 2009; DOI: 10.1007/s00213-009-1549-9
The Science Daily article on Kava and liver toxicity explains the changes noticed in the liver, but does not explain why the changes noticed are "bad" per se.
I do find it incredibly interesting that the Australian study pinpoints the chemical vs. natural extract processing as the key to whether kava has a negative impact on the liver. I've seen this concept cross over into many different things - such as the corn syrup debate. To my knowledge, we couldn't have corn syrup through any "natural" processing method - it's chemically extracted, and actually how a lot of the corn syrups out of there become contaminated with mercury in the process. The growing evidence that organic farming is superior to the synthetic fertilization/pesticide cycles - etc.
Flax seed oil
May reduce absorption of some medications and supplements. This research does not mention SAMe specifically, but it cautions against comsuming flax seed oil with various mood-altering herbs in general, such as St. John's Wort.
More information and preventative measures explained below:
Interactions with Drugs
Taking flaxseed ( not flaxseed oil) by mouth may reduce the absorption of other medications. Drugs used by mouth should be taken one hour before or two hours after flaxseed to prevent decreased absorption. People taking mood stabilizers such as lithium should use caution. Flaxseed contains alpha-linolenic acid, which may theoretically lower blood pressure. Individuals taking medications to lower blood pressure should use caution when taking flaxseed. Laxatives and stool softeners may increase or enhance the laxative effects of flaxseed. Flaxseed and flaxseed oil can lower cholesterol levels in animals, but studies in humans show mixed results. In theory, flaxseed may increase the effect of other medications that lower lipid (cholesterol and triglyceride) levels in the blood. Hormonal drugs may be affected. Dietary flaxseed may increase the effects of tamoxifen, a medication used to treat cancer. Consult a qualified oncologist and pharmacist before making decisions about treatment or health conditions.
Although studies report conflicting results, the omega-3 fatty acids in flaxseed and flaxseed oil may increase blood sugar, reducing the effects of diabetes treatments, including insulin and glucose-lowering medications taken by mouth. Flaxseed ( not flaxseed oil) is a rich source of plant lignans. Lignans are sometimes referred to as phytoestrogens and may possess estrogen-like properties. It is not known if flaxseed can alter the effects of birth control pills or hormone replacement therapies. Flaxseed and flaxseed oil theoretically may increase the risk of bleeding, and caution should be used when flaxseed products are taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin ® ) or heparin, anti-platelet drugs such as clopidogrel (Plavix ® ), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin ® , Advil ® ) or naproxen (Naprosyn ® , Aleve ®).
Flaxseed may also interact with muscle relaxants (such as metaxalone), drugs used for acid reflex (proton pump inhibitors such as lansoprazole), or prostaglandins (such as Iloprost or treprostinil).
Interactions with Herbs and Dietary Supplements
Consumption of flaxseed ( not flaxseed oil) may reduce the absorption of vitamins or supplements taken by mouth at the same time. Therefore, vitamins and supplements should be taken an hour before or two hours after a dose of flaxseed to prevent decreased absorption. Flaxseed may alter the effects of psyllium and vitamin E in particular.
Use caution if combining flaxseed with other mood-altering herbs, including St. John's wort ( Hypericum perforatum ), kava ( Piper methysticum ), or valerian ( Valeriana officinalis ). Hormonal herbs and supplements may be affected. Flaxseed contains alpha-linolenic acid, which may theoretically lower blood pressure. Use caution when combining flaxseed with other herbs or supplements that can lower blood pressure.
Because of the laxative effects of flaxseed, caution should be used when it is taken with other supplements that have laxative effects.
Studies on the effects of flaxseed on blood sugar in people with type 2 diabetes report mixed results. Use caution when combining flaxseed products with supplements that may raise blood sugar levels. In theory, flaxseed may contain estrogen-like chemicals. Use caution when combining flaxseed ( not flaxseed oil) with supplements believed to have estrogen-like properties.
Early studies in humans show that flaxseed and flaxseed oil theoretically may increase the risk of bleeding. Caution should be used when flaxseed products are taken with herbs and supplements that are believed to increase the risk of bleeding.
Flaxseed may lower blood cholesterol levels. Caution is advised when using herbs or supplements that may also lower cholesterol. Cholesterol levels may require monitoring, and doses may need adjustment.
Use cautiously when taking flax with other herbs or supplements taken to treat or prevent cancer due to a possible interaction.
Thanks for posting, DL
B12
When using SAMe, it's often necessary to supplement with B vitamins. Things to note and look for concerning vitamin B12 as referenced from a Mercola product ad, just to start.
What B12 does for you...
Vitamin B-12 helps folic acid regulate the formation of red blood cells, and helps your body use iron*.
In addition, it is also needed for proper digestion, food absorption, carbohydrate and fat metabolism.* It also helps keep your nervous system healthy by assisting the nerves of your body to function and communicate in an optimal manner.*
B-12 also helps in cell formation and cellular longevity.* Plus, it can support female reproductive health, and promote normal nerve growth and development by maintaining the fatty sheaths.* These fatty sheaths play a vital role as they cover and protect your nerve endings.*
What's more, this workhorse of a micronutrient is critical to your circulation and adrenal hormone production -- plus, it helps boost your immunity.*
Vitamin B-12 supports a healthy mood and feelings of well-being.* And then there's this -- it also provides excellent support for your memory, mental clarity, and concentration.*
B-12 plays a vital role in melatonin production.* Melatonin has been called "the sleep hormone" because it is responsible for letting you get a good night's sleep.
(It's good for more than just an "energy boost")
How You Become Vitamin B12 Deficient
The older you get the more likely you are to have a vitamin B12 deficiency because your body becomes less efficient at making this hormone. The two ways that you become deficient in vitamin B12 are from not getting enough in your diet and from losing the ability to absorb it.
I recently visited India which is primarily a vegetarian based culture and current studies there show about 80% of the adults are deficient in vitamin B12. However, vegans are not the only ones who can become vitamin B12 deficient.
The older you get the more your digestive system breaks down, especially if you have been following the standard American diet. Specifically the lining of your stomach gradually loses its ability to produce hydrochloric acid which releases vitamin B 12 from your food. The use of antacids or anti ulcer drugs will also lower your stomach acid secretion and decrease your ability to absorb vitamin B 12. Infection with Helicobactor pylori, a common contributor to stomach ulcers, can also result in vitamin B12 deficiency.
However the main cause of vitamin B 12 deficiency is a term researchers call food-cobalamin malabsorption syndrome. Cobalamin is the scientific term for vitamin B12. This typically results when your stomach lining loses its ability to produce intrinsic factor which is a protein that binds to vitamin B12 and allows your body to absorb it at the end of your small intestine.
B-12 needs the help of a protein in order to be absorbed. That protein is called intrinsic factor. And because the lining of your stomach makes intrinsic factor, people with less-than-optimal gastrointestinal health often need to supplement with B-12.*
B-12 Deficiency causes the following symptoms
* Tiredness and feelings of weakness...*
* Less-than-optimal nervous system functioning...*
* Less-than-optimal eye health...*
* Loss of appetite and unintended weight loss...*
* Occasional constipation and gas...*
* Feelings of mild moodiness...*
* Less-than-optimal memory...*
* A tendency toward nervousness...*
* Less-than-optimal balance...*
* Less-than-optimal liver or heart health...*
* Premature grey hair...
* Occasional digestive issues...
REFERENCES
1. How Common is Vitamin B-12 Deficiency? American Journal of Clinical Nutrition, Vol. 89, No. 2, 693S-696S, February 2009
2. An Update on Cobalamin Deficiency in Adults Quarterly Journal of Medicine 102(1):17-28; 2009
3. Vitamin B12 and Health Canadian Family Physician Vol. 54, No. 4, April 2008, pp.536 - 541
I've not read up on the intrinsic factor (IF) protein that facilitates the B12 absorption, but I plan to double check the science on the Figure he presents:
Figure 1. Cobalamin (cbl) absorption and metabolic pathway. (A) Structure of cobalamin (vitamin B12) with a corrin ring bound to a central cobalt atom. (B) The metabolic journey of cbl from nutrient intake to its intestinal absorption. Endocytic receptors and proteins responsible for vitamin B12 intestinal absorption include cubilin (CUBN), amnionless (AMN), receptor-associated protein (RAP) and megalin (LRP-2). The membrane megalin/transcobalamin II (TCII) receptor complex allows the cellular uptake of cbl. Lysosomal-mediated degradation of TCII and subsequent release of free cbl is essential for vitamin B12 metabolic functions. MS: methonine synthase; THF: tetrahydrofolate; MTHFR: methyltetrahydrofolate reductase; MCM: methylmalonyl coA mutase.
Listed on the page are sources of B12, but he references them to mention that "you can eat all these and still be deficient". I'll have to sort out which part of that is sales pitch, and what part of it's true since I've seen conflicting evidence about the topic of good food sources for B12.
A few Dr. Mercola listed are:
Meat, poultry, lamb's liver, brewer's yeast, clams, eggs, herring, mackerel, kidneys, milk, dairy products, or seafood.
I've read that certain seaweeds are good for this too. (Go directly to the marine source.)
As far as meat goes, vitamin B12 is actually a soil bacteria that gets ingested by an animal and this is how it ends up in the meat, so not all meat has B12 just intrinsically. Theoretically humans could get B12 from the very same place that cows do.
Hopefully more to come...
SAMe and homocystine
I've been thinking about this topic and reports of people who have attempted to use SAMe to combat their depression by regulating there seratonin cycles.
One side effect of using SAMe is commonly described as a feeling of being agitated. Sometimes to an extreme level. Other anti depressants have the same side effects. The page link above calls it "seratonin toxicity".
Wiki describes the symptoms:
* Cognitive effects: mental confusion, hypomania, hallucinations, agitation, headache, coma
* Autonomic effects: shivering, sweating, hyperthermia, hypertension, tachycardia, nausea, diarrhea.
* Somatic effects: myoclonus (muscle twitching), hyperreflexia (manifested by clonus), tremor.
I take a couple steps back and consider the digestive process in all of this again. In taking SAMe, you're helping the part of the digestive system that biosynthesizes methionine (the methylation process).
That methionin can be converted to L-cystine.
Eventually the goal in the digestive process is that this is further utilized to create glutathione. Which detoxifies any xenobiotics, supports liver health etc.
SAMe is also a precursor to seratonin production. That's presumedly what happens when everything goes smoothly with SAMe supplementation.
The trouble is that homocystine is also biosynthesized from methionine.
If this is not addressed high homocystine has been linked to elevated cholesterol and hypertension.
"Anger and hostility correlate with the risk of heart disease.7 8 A preliminary study found a link between high homocysteine levels and hostility and repressed anger.9 While anger, hostility, high homocysteine, and heart disease all appear to be tied together, which of these is cause and which is effect remains somewhat unclear."
I'm thinking that there's a correlation between the feelings of agitation - the symptoms of seratonin toxicity and the symptoms of high homocysteine levels.
I wonder if the people who develop seratonin toxicity from SAMe are the cases where the individuals have a lot of xenotoxins to remove from their system. The first phase of the breakdown occurs in the liver, but there are not enough raw materials to continue processing/eliminating the toxins that precipitate. Utilizing B vitamins must help to prevent/remedy some of that.
(Here's a website that explains the detoxification process)
"Homocysteine can be recycled into methionine or converted into cysteine with the aid of B-vitamins.
It's not just as easy as taking mass amounts of B vitamins though... they need to be taken in the correct ratios.
Taking more than 1,000 mg of niacin (B3) a day can raise homocysteine levels, especially if niacin is not balanced by folic acid (B9) (400-1,000 mg a day), vitamin B6 (10-50 mg a day), and vitamin B12 (50-300 micrograms a day). If you take more than 1,000 mg of niacin daily, you need additional B vitamins.
Relating to the lowering of homocystine levels...
By many doctors it is suggested to take 1,000 mcg of folic acid, 50 to 150 mg of vitamin B12, and 25 to 50 mg of vitamin B6. If you are one of those individuals who does not totally respond to B vitamins, you can consider adding Betaine (Trimethylglycine or TMG) to reduce your homocysteine levels. It is recommend starting with 1 gram daily and building up to as much as 5 to 6 grams if necessary to get your homocysteine level down below 7, or at least below 8.
(General information on some of the B vitamins from this vitacost site)
Riboflavin (B2) activates B6 (PLP, Pyridoxal-5’-Phosphate, Pyridoxine)B6 helps to make and take apart many amino acids and is also needed to make the hormones, serotonin, melatonin, and dopamine.
B9 (Folate, Methylfolate): Folic acid is a B vitamin needed for cell replication and growth. Folic acid helps form building blocks of DNA, the body’s genetic information, and building blocks of RNA, needed for protein synthesis in all cells. Therefore, rapidly growing tissues, such as those of a fetus, and rapidly regenerating cells, like red blood cells and immune cells, have a high need for folic acid. Used for depression and schizophrenia.