![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by jrbecker on November 14, 2004, at 14:06:26
the response rates from this study on adjunctive SAMe are fairly good, too bad it's so expensive...
Volume 24(6) December 2004 pp 661-664
S-Adenosyl-L-Methionine (SAMe) as an Adjunct for Resistant Major Depressive Disorder: An Open Trial Following Partial or Nonresponse to Selective Serotonin Reuptake Inhibitors or VenlafaxineAlpert, Jonathan E. MD, PhD*; Papakostas, George MD*; Mischoulon, David MD, PhD*; Worthington, John J. III MD*; Petersen, Timothy PhD*; Mahal, Yasmin BA*; Burns, Alana BA*; Bottiglieri, Teodoro PhD†; Nierenberg, Andrew A MD*; Fava, Maurizio MD*
*Depression Clinical and Research Program, Massachusetts General Hospital, Department of Psychiatry, Harvard Medical School, Boston, MA and †Baylor Institute of Metabolic Disease, Dallas, TX.
Received December 11, 2003; accepted after revision June 28, 2004.
Address correspondence and reprint requests to Jonathan E. Alpert, MD, PhD, Massachusetts General Hospital, Depression Clinical and Research Program, 50 Staniford Street, 4th floor, Boston, MA 02114. E-mail: jalpert@partners.org.
--------------------------------------------------------------------------------Abstract
Background: The purpose of this open trial was to evaluate the safety, tolerability, and efficacy of oral S-adenosyl-l-methionine as an antidepressant adjunct among partial and nonresponders to serotonin reuptake inhibitors or venlafaxine.Method: Thirty antidepressant-treated adult outpatients with persisting major depressive disorder received 800 to 1600 mg of S-adenosyl-l-methionine tosylate over a 6-week trial.
Results: Intent-to-treat analyses based on the Hamilton Depression Rating Scale revealed a response rate of 50% and a remission rate of 43% following augmentation with S-adenosyl-l-methionine. Gastrointestinal symptoms and headaches were the most common side effects.
Conclusion: Augmentation of selective serotonin reuptake inhibitors or venlafaxine with S-adenosyl-l-methionine warrants a placebo-controlled trial in resistant depression.
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Acommon clinical strategy when first-line antidepressants fail is to add a second agent with established or putative antidepressant properties, including bupropion, dopamine agonists (eg, pramipexole), psychostimulants (eg, methylphenidate), lithium, thyroid, buspirone, or pindolol.1,2 Dietary supplements, widely used among patients with mood and anxiety disorders,3 have also been studied for their possible role in enhancing or speeding response to antidepressants. These supplements include the omega-3 fatty acids,4,5 inositol,6 and folate.7,8 Anecdotal experience suggests a potential role for S-adenosyl-l-methionine (SAMe) in antidepressant augmentation.9 The purpose of this study was to evaluate the safety, tolerability, and efficacy of SAMe when added to selective serotonin reuptake inhibitor (SSRI) antidepressants or venlafaxine among adults with unremitted depression.Although first marketed in the United States in 1999, SAMe has been available in parenteral and oral forms for treatment of depression in Europe since the 1970s. Enteric-coated oral preparations of SAMe (SAMe tosylate or SAMe butanedisulphonate [SD4]) have helped address problems of stability that plagued previous formulations.10,11 The recent metaanalysis of placebo-controlled SAMe trials for depression (n = 422; 7 parenteral, 4 oral) commissioned by the Agency for Healthcare Research and Quality 12 showed an overall reduction of approximately 6 points over placebo in the Hamilton Depression Rating Scale (HAM-D) score (17- or 21-item) at 3 weeks, suggesting a clinically significant albeit partial response. Similarly, metaanalysis of double-blind trials involving an active comparator (n = 1,015; 10 parenteral, 4 oral) showed that SAMe was associated with no statistically significant difference in outcomes compared to treatment with tricyclic antidepressants,12 reinforcing similar conclusions from an earlier metaanalysis by Bressa.13 However, not all of these trials were adequately powered to discern a difference between SAMe and the tricyclics, some used only low to moderate doses of the tricyclics, and a majority involved parenteral formulations of SAMe.
To our knowledge, the only published report of combining SAMe with an SSRI in a controlled trial is that by Chinchilla and colleagues 14 whose study suggested that supplementation with SAMe (100 mg im vs. placebo) shortened the latency of response to fluoxetine (20 mg). A similar claim was made for the combination of SAMe (200 mg im vs. placebo) with imipramine (150 mg po).15 A case report, however, describes altered mentation, fever, hyperreflexia, and elevated creatinine phosphokinase when SAMe (100 mg im) was combined with the tricyclic antidepressant, clomipramine (75 mg), in a 71-year-old woman.16 Although similar symptoms suggesting serotonin syndrome have not been described in previous controlled studies on the efficacy and safety of SAMe administered in conjunction with older antidepressant agents including maprotiline,17 or mianserin 18 and a case report involving addition of SAMe to phenelzine,9 further information is clearly needed regarding the safety and tolerability, as well as efficacy, for the rational use of oral SAMe for antidepressant augmentation.
MATERIALS AND METHODS
Sample
Forty-five consecutive study volunteers (ages 18 to 75) drawn from an outpatient sample of antidepressant-treated adults with persisting depressive symptoms were enrolled for screening at 1 of 3 primary care sites and at the Depression Clinical and Research Program. Subjects at the 3 primary care sites were generally outpatients already receiving medical treatment at those sites. Subjects at the Depression Clinical and Research Program were referred clinically or responding to study advertisements. Subjects were required to be on a stable (>=4 weeks), minimally adequate dose of an SSRI or venlafaxine (fluoxetine/paroxetine/citalopram >=20 mg/d, escitalopram >=10 mg/d, sertraline >=50 mg/d, or venlafaxine >=75 mg/d). They needed to meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for current major depressive disorder and have a HAM-D-17 19 score of >=14 at screening and baseline visits. Exclusions included active suicidality, bipolar disorder, psychosis, and pregnancy as well as repeated antidepressant resistance (>3 adequate antidepressant trials) during the current major depressive disorder episode, and use of concomitant dietary supplements with putative antidepressant or mood-stabilizing activity.Treatment
Eligible subjects were evaluated weekly for 4 weeks and had a final visit at the end of week 6. Based upon doses used in previous SAMe clinical trials for depression, osteoarthritis, and cirrhosis,10,12 SAMe tosylate (Nature Made® supplied by Pharmavite, LLC) was started at 400 mg bid and was increased to 800 mg bid after 2 weeks. Subjects could remain on or return to the initial dose based upon clinical judgment. SSRI and venlafaxine doses could be lowered within the therapeutic range, if clinically indicated, while subjects requiring an increased antidepressant dose were discontinued.Efficacy, Tolerability, and Safety Measures
Response was defined as a 50% reduction in HAM-D-17 score from baseline to end point. Remission was defined as a final HAM-D-17 score of <=7. Secondary efficacy measures included the Montgomery Asberg Depression Rating Scale 20 and the Clinical Global Impressions-Severity and Improvement scales 21 and the 90-item Kellner Symptom Questionnaire (SQ).22 Paired t tests were conducted on baseline and end point assessments. The primary assessment of tolerability was the number of dropouts attributed to side effects. Sexual dysfunction at baseline and end point was assessed by the validated Massachusetts General Hospital Sexual Function Questionnaire.23Pretreatment and posttreatment serum homocysteine levels were measured given the interrelationship between SAMe and homocysteine in the 1-carbon cycle and concern about the increased risk of vasoocclusive disease with hyperhomocysteinemia.24 Baseline serum B12, homocysteine, and serum and red blood cell folate were also determined to evaluate the hypothesis that low folate and/or high homocysteine would be associated with a favorable response to SAMe augmentation based on their links in the 1-carbon cycle.11
RESULTS
Thirty of 45 subjects who were screened were eligible for the study and proceeded to baseline evaluation. The mean age for all patients was 48.4 ± 13.0 (SD) years and the gender distribution was 22/30 (73.3%) females. The mean duration of the current major depressive episode was 20.3 ± 29.0 months. The mean number of lifetime major depressive episodes was 4.0 ± 3.8. The mean age of onset of major depressive disorder in years was 28.7 ± 11.5. The mean total HAM-D-17 and Clinical Global Impressions-Severity scores during the baseline visit were 17.7 ± 4.2 (median 17.0, range 14 to 26) and 4.0 ± 0.7, respectively. Overall, 10 patients enrolled had a major depressive episode resistant to fluoxetine (mean dose 43.0 ± 21.1 mg), 2 to sertraline (mean dose 150.0 ± 70.7 mg), 13 to citalopram (mean dose 48.4 ± 32.6 mg), 1 to escitalopram (20 mg), 1 to paroxetine (40 mg), and 3 to venlafaxine (mean dose 200.0 ± 86.6 mg). The mean duration of the failed SSRI/venlafaxine trial was 14.5 ± 14.4 months (median 11.5 months; range 2 to 55 months). All but 4 patients had failed to respond to SSRI/venlafaxine doses higher than the required minimum to enroll in the study, and all patients had failed to respond to an SSRI trial at least twice as long as the minimally required 4 weeks.Twenty-three (76.6%) of 30 subjects completed the 6-week trial. The most common adverse events are listed in Table 1. Two subjects (6.6%) discontinued early because of intolerance of study treatment. No patient experienced a serious adverse event including serotonin syndrome.
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TABLE 1. Common Side Effects of SAMe 800 to 1600 mg/d*--------------------------------------------------------------------------------
There was a significant but modest (4.9%) decrease in pretreatment to posttreatment homocysteine levels (from 8.2 ± 2.5 to 7.8 ± 2.3 µmol/L, t test; df = 22; P = 0.003). There was also a small but significant reduction in Massachusetts General Hospital Sexual Function Questionnaire scores reflecting improvement, (22.8 ± 6.4 vs. 20.6 ± 7.3; df = 29; P = 0.02). There was no significant weight change over 6 weeks (183.1 ± 55.3 lb vs. 183.9 ± 56.8 lb, respectively; P > 0.05).
Intent-to-treat (ITT) analysis with last observation carried forward indicated a significant decrease in depression severity from baseline to end point as measured by the HAM-D-17 (17.7 ± 4.2 to 10.0 ± 6.6, df = 29; P < 0.0001), the Montgomery Asberg Depression Rating Scale (23.2 ± 6.2 to 13.9 ± 8.4, df = 29; P < 0.0001), and the Beck Depression Inventory (18.8 ± 5.4 to 12.2 ± 8.6, df = 29; P = 0.0002). There was also a significant decrease in Clinical Global Impressions-Severity scores, baseline to end point (4.0 ± 0.7 to 2.7 ± 1.2, df = 29; P < 0.0001). At end point, there were 15 (50.0%) responders and 13 (43.3%) remitters in the ITT analysis. At end point, there were 13 (56.5%) responders and 11 (47.8%) remitters in the completer analysis. Figure 1 presents mean HAM-D-17 scores by week for ITT and completer group samples.
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FIGURE 1. Change in mean HAM-D-17 scores. P < 0.0001 paired t test for all postbaseline HAM-D-17 severity assessments when compared to baseline HAM-D-17 severity for both ITT and Completer Analysis.--------------------------------------------------------------------------------
There was also a statistically significant improvement in baseline to end point SQ-depression scores (13.2 ± 4.9 vs. 7.5 ± 5.3, respectively, t test; df = 29; P = 0.001) and SQ-anxiety scores (12.2 ± 4.9, vs. 8.0 ± 5.6, respectively; df = 29; P = 0.012), but not SQ-anger/hostility scores (8.2 ± 5.6 vs. 5.8 ± 5.8, respectively; df = 29; P = 0.14), SQ-somatic symptom scores (10.6 ± 5.5 vs. 9.1 ± 6.1; P > 0.05), or SQ-somatic well-being scores (1.7 ± 1.9 vs. 2.7 ± 2.8, respectively, P > 0.05) in the ITT sample.
Low baseline folate (<=5.65) or B12 (<=148.1) levels, or elevated homocysteine levels (>=13.2) were not associated with positive clinical response to SAMe augmentation in this limited sample (P > 0.05 for all analyses); similarly, mean levels of folate, B12, or homocysteine did not differ between responders and nonresponders.
DISCUSSION
Consistent with the earlier findings of Chinchilla et al 14 who combined parenteral SAMe with fluoxetine, the combination of oral enteric-coated SAMe with SSRIs or venlafaxine for antidepressant augmentation was generally well tolerated. Additionally, there was evidence for a slight decrease in serum homocysteine consistent with the limited previous literature 25,26 as well as reduction of sexual dysfunction on SSRIs (perhaps related to the putative dopaminergic enhancement by SAMe 27,28). Preliminary evidence for efficacy were ITT response and remission rates comparable to those recently reported for bupropion augmentation of SSRIs or venlafaxine 29 as well as for switching to other antidepressants such as venlafaxine or mirtazapine after initial treatment resistance.30,31 Response and remission rates exceeded those in a very similar previous trial we conducted on folinic acid.8 Limitations of this study are its small sample size, lack of a placebo control, unblinded assessments, and inclusion of subjects whose antidepressant monotherapy had not been prospectively optimized. In addition, stability studies were not conducted on the SAMe tablets used for this trial and dose-finding studies are needed to identify whether the higher and therefore more costly doses used in this study are, in fact, necessary for efficacy. Nevertheless, within the limits of an uncontrolled trial, the results of this preliminary study suggest that the combination of SAMe with antidepressants deserves further scrutiny as a potentially safe and effective addition to the growing armamentarium of treatment approaches to resistant depression.ACKNOWLEDGMENTS
This study was funded by Pharmavite, LLC, a distributor of SAMe products. We also thank Marc Alan Pfeffer, MD, PhD, and Courtney Vitale of Partners Research and Education Program (PREP) for their support in conducting this study.REFERENCES
1. Fava M. Psychopharmacological management of residual symptoms and treatment resistance in major depressive disorder. In: Alpert JE, Fava M, eds. Handbook of Chronic Depression. New York: Marcel Dekker Inc.; 2003:257-279. [Context Link]2. Nelson JC. Managing treatment-resistant major depression. J Clin Psychiatry. 2003;64(suppl 1):5-12. Library Holdings Bibliographic Links [Context Link]
3. Kessler RC, Soukup J, David RB, et al. The use of complementary and alternative therapies to treat anxiety and depression in the United States. Am J Psychiatry. 2001;158:289-294. Ovid Full Text Library Holdings Bibliographic Links [Context Link]
4. Nemets B, Stahl ZM, Belmaker RH. Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry. 2002;159:477-479. Ovid Full Text Library Holdings Bibliographic Links [Context Link]
5. Su K, Huang S, Chiu C, et al. Omega-3 fatty acids in major depressive disorder: a preliminary double-blind, placebo controlled trial. Eur Neuropsychopharmacol. 2003;13:267-271. Library Holdings Bibliographic Links [Context Link]
6. Levine J, Mishori A, Susnosky M, et al. Combination of inositol and serotonin reuptake inhibitors in the treatment of depression. Biol Psychiatry. 1999;45(3):270-273. Full Text Library Holdings Bibliographic Links [Context Link]
7. Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomized, placebo controlled trial. J Affect Disord. 2000;60(2):121-130. Full Text Library Holdings Bibliographic Links [Context Link]
8. Alpert JE, Mischoulon D, Rubenstein GEF, et al. Folinic acid (Leucovorin) as an adjunctive treatment for SSRI-refractory depression. Ann Clin Psychiatry. 2002;14(1):33-38. [Context Link]
9. Brown R, Gerbarg P, Bottiglieri T. S-adenosylmethionine (SAMe) for depression. Psychiatr Ann. 2002;32:44. [Context Link]
10. Chavez M. SAMe: S-adenosylmethionine. Am J Health-Syst Pharm. 2000;57:119-123. [Context Link]
11. Mischoulon D, Fava M. Role of S-adenosyl-l-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr. 2002; 76(suppl):1158S-1161S. [Context Link]
12. Hardy M, Coulter I, Morton SC, et al. S-adenosyl-l-methionine for treatment of depression, osteoarthritis, and liver disease [Agency for Healthcare Research and Quality Web site]. October 2002. Available at: http://www.ahrq.gov . Accessed September 17, 2003. [Context Link]
13. Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl. 1994;154:7-14. Library Holdings Bibliographic Links [Context Link]
14. Chinchilla MA, Vega PM, Cebollada GA, et al. Latencia antidepresiva y S-adenosil-metionina. An Psiquiatr. 1996;12:67-71. [Context Link]
15. Berlanga C, Ortega-Soto HA, Ontiveros M, et al. Efficacy of S-adenosyl-l-methionine in speeding the onset of action of imipramine. Psychiatry Res. 1992;44(3):257-262. Library Holdings Bibliographic Links [Context Link]
16. Iruela LM, Minguez L, Merino J, et al. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry. 1993;150:522. Library Holdings Bibliographic Links [Context Link]
17. Rabassini A, Russo G. Effetti dell'associazione maprotilina SAMe nelle sindromi depressive (studio controlato in dopio cieco). Estratto dalla Rivsita: Psichiatria Generale e dell'eta Evolutiva. 1979;3:305-323. [Context Link]
18. Alvarez E, Udina C, Guillamat R. Shortening of latency period in depressed patients treated with SAMe and other antidepressant drugs. Cell Biol Rev. 1987;S1:103-110. [Context Link]
19. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56-62. [Context Link]
20. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382-389. [Context Link]
21. In: Guy W, ed. ECDEU Assessment Manual for Psychopharmacology, revised. DHEW Pub. No. (ADM) 76-338. Rockville, MD: National Institute of Mental Health; 1976. [Context Link]
22. Kellner R. A symptom questionnaire. J Clin Psychiatry. 1987;48: 268-274. Library Holdings Bibliographic Links [Context Link]
23. Labbate LA, Lare SB. Sexual dysfunction in male psychiatric outpatients: validity of the Massachusetts General Hospital Sexual Functioning Questionnaire. Psychother Psychosom. 2001;70:221-225. Library Holdings Bibliographic Links [Context Link]
24. Lee R, Frenkel EP. Hyperhomocysteinemia and thrombosis. Hematol Oncol Clin North Am. 2003;17:85-102. Library Holdings Bibliographic Links [Context Link]
25. Loehrer FM, Schwab R, Angst CP, et al. Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans. J Pharmacol Exp Ther. 1997;282:845-850. Library Holdings Bibliographic Links [Context Link]
26. Ueland PM, Refsum H, Stabler SP, et al. Total homosysteine in plasma or serum: methods and clinical applications. Clin Chem. 2003; 39:1764-1779. [Context Link]
27. Worthington JJ III, Simon NM, Korbly NB, et al. Ropinirole for antidepressant-induced sexual dysfunction. Int Clin Psychopharmacol. 2000;17:307-310. [Context Link]
28. Bottiglieri T, Laundy M, Crellin R, et al. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry. 2000;69:228-232. Ovid Full Text Full Text Library Holdings Bibliographic Links [Context Link]
29. DeBattista C, Solvason HB, Poirier J, et al. A prospective trial of bupropion SR augmentation of partial and non-responders to serotonergic antidepressants. J Clin Psychopharmacol. 2003;23:27-30. [Context Link]
30. Nierenberg AA, Feighner JP, Rudolph R, et al. Venlafaxine for treatment-resistant unipolar depression. J Clin Psychopharmacol. 1994; 14:419-423. Library Holdings Bibliographic Links [Context Link]
31. Fava M, Dunner DL, Greist JH, et al. Efficacy and safety of mirtazapine in major depressive disorder patients after SSRI treatment failure: an open-label trial. J Clin Psychiatry. 2001;62:413-420. Library Holdings Bibliographic Links [Context Link]
Posted by KaraS on November 14, 2004, at 14:06:26
In reply to SAMe augmentation for resistant MDD, posted by jrbecker on November 13, 2004, at 19:22:06
You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
Posted by SLS on November 14, 2004, at 14:06:27
In reply to Re: SAMe augmentation for resistant MDD » jrbecker, posted by KaraS on November 13, 2004, at 23:36:28
> You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
Do you know what the monthly cost of this would be?
- Scott
Posted by raybakes on November 14, 2004, at 15:53:12
In reply to Re: SAMe augmentation for resistant MDD » jrbecker, posted by KaraS on November 13, 2004, at 23:36:28
> You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
Personally think that SAMe supplements are dangerous without B12, folate and TMG - SAMe goes straight to homocysteine and then depletes our methyl donors - does anyone else think the same?
Ray
Posted by KaraS on November 14, 2004, at 17:31:12
In reply to Re: SAMe augmentation for resistant MDD » KaraS, posted by raybakes on November 14, 2004, at 15:53:12
> > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
>
> Personally think that SAMe supplements are dangerous without B12, folate and TMG - SAMe goes straight to homocysteine and then depletes our methyl donors - does anyone else think the same?
>
> Ray
>Yes, I believe that Larry made an impressive case for that in earlier posts. Actually, he recommended the TMG plus B12 (and folate?) without the SAM-e at all. I'm sure if you did a search, you'd find them.
Kara
Posted by KaraS on November 14, 2004, at 17:40:50
In reply to Re: SAMe augmentation for resistant MDD, posted by SLS on November 14, 2004, at 7:05:47
> > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
>
> Do you know what the monthly cost of this would be?
>
>
> - Scott
It's quite a bit cheaper than SAM-e. I need to find Larry's old posts to see about the dosage range of TMG + B12 he recommends so I could give you some accurate figures. You might need to add in folate to balance the B12 as well. SAM-e works for some people in varrying dosages - anywhere from 200-1600 mg. a day - so your cost would vary considerably based on dosage required.I'll do a little searching for those old posts later and get back to you on this (assuming that Larry or someone else doesn't get to it first).
K
Posted by JLx on November 14, 2004, at 17:59:24
In reply to Re: SAMe augmentation for resistant MDD, posted by KaraS on November 14, 2004, at 17:40:50
> > > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
> >
> > Do you know what the monthly cost of this would be?
> >
> >
> > - Scott
>
>
> It's quite a bit cheaper than SAM-e. I need to find Larry's old posts to see about the dosage range of TMG + B12 he recommends so I could give you some accurate figures. You might need to add in folate to balance the B12 as well. SAM-e works for some people in varrying dosages - anywhere from 200-1600 mg. a day - so your cost would vary considerably based on dosage required.
>
> I'll do a little searching for those old posts later and get back to you on this (assuming that Larry or someone else doesn't get to it first).
>
>
> K
>Here's one thread from a year ago: http://www.dr-bob.org/babble/alter/20031104/msgs/278139.html There's a lot of info in Larry's posts there. DSCH also makes an important note, I think, that it was magnesium that "turned on" TMG for him.
TMG is availble through Beyond a Century in bulk form, so inexpensive that way. It's tolerable tasting dissolved in water.
JL
Posted by JLx on November 14, 2004, at 18:42:34
In reply to Re: SAMe augmentation for resistant MDD, posted by JLx on November 14, 2004, at 17:59:24
> > > > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
> > >
> > > Do you know what the monthly cost of this would be?
> > >
> > >
> > > - Scott
> >
> >
> > It's quite a bit cheaper than SAM-e. I need to find Larry's old posts to see about the dosage range of TMG + B12 he recommends so I could give you some accurate figures. You might need to add in folate to balance the B12 as well. SAM-e works for some people in varrying dosages - anywhere from 200-1600 mg. a day - so your cost would vary considerably based on dosage required.
> >
> > I'll do a little searching for those old posts later and get back to you on this (assuming that Larry or someone else doesn't get to it first).
> >
> >
> > K
> >
>
> Here's one thread from a year ago: http://www.dr-bob.org/babble/alter/20031104/msgs/278139.html There's a lot of info in Larry's posts there. DSCH also makes an important note, I think, that it was magnesium that "turned on" TMG for him.
>
> TMG is availble through Beyond a Century in bulk form, so inexpensive that way. It's tolerable tasting dissolved in water.
>
> JLI was reading over that old thread...so glad to have this documentation sometimes! I see I was taking about 800 mg of TMG 3 times a day. I didn't realize it was so much and though I have been taking it again lately, not that much. I was feeling loads better in those days too.
I have noticed that taking the TMG feels different since I've been taking MSM, but again maybe I'm not taking enough. What exactly is the relation to TMG and MSM, other than that they are methyl donors? I usually take 1-2,000 mg of MSM, though I've been slacking off lately. Hmm...maybe this is why I feel more crappy.
This board is so helpful. :)
"Research has found that TMG is converted into SAM in the body. TMG is less expensive than SAM.
Dosage: 3,000 milligrams a day, followed by a maintenance dose of 1,000 milligrams a day for up to three weeks." http://www.holistic-online.com/Remedies/Depression/dep_nutrition2.htm#TMGI'm reading "Optimum Nutrition for the Mind" and Patrick Holford recommends TMG 600-2000 mg daily on an empty stomach or with fruit.
JL
Posted by JLx on November 14, 2004, at 18:54:55
In reply to Re: SAMe augmentation for resistant MDD, posted by KaraS on November 14, 2004, at 17:40:50
> > > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
> >
> > Do you know what the monthly cost of this would be?
> >
> >
> > - Scott
>
>
> It's quite a bit cheaper than SAM-e. I need to find Larry's old posts to see about the dosage range of TMG + B12 he recommends so I could give you some accurate figures. You might need to add in folate to balance the B12 as well. SAM-e works for some people in varrying dosages - anywhere from 200-1600 mg. a day - so your cost would vary considerably based on dosage required.
>
> I'll do a little searching for those old posts later and get back to you on this (assuming that Larry or someone else doesn't get to it first).
>
>
> K
>I see in the long running "Supplements for Brain Fog" thread http://www.dr-bob.org/babble/alter/20040613/msgs/363881.html that you said in July that you were might try TMG and that you were also taking Rhodiola? How did either of those work?
JL
Posted by KaraS on November 14, 2004, at 19:01:50
In reply to Re: SAMe augmentation for resistant MDD, posted by SLS on November 14, 2004, at 7:05:47
> > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
>
> Do you know what the monthly cost of this would be?
>
>
> - Scott
Looking through Larry's old posts (and using JLx's suggestion of bulk purchase at BeyondACentury), he claims that the dosage for TMG is 1-8 grams per day. He could tolerate no more than 1 gram a day so best to start out slow. I don't see where he gave any amounts for B12 or folate. The TMG itself in bulk form at BAC would run $6.50 for 150 grams. Even once you add in tax, shipping and some B vitamins, it's a hell of a lot cheaper (and probably safer) than SAM-e.K
Posted by JLx on November 14, 2004, at 19:18:31
In reply to Re: TMG dosage and cost - quick summary, posted by KaraS on November 14, 2004, at 19:01:50
> > > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
> >
> > Do you know what the monthly cost of this would be?
> >
> >
> > - Scott
>
>
> Looking through Larry's old posts (and using JLx's suggestion of bulk purchase at BeyondACentury), he claims that the dosage for TMG is 1-8 grams per day. He could tolerate no more than 1 gram a day so best to start out slow. I don't see where he gave any amounts for B12 or folate. The TMG itself in bulk form at BAC would run $6.50 for 150 grams. Even once you add in tax, shipping and some B vitamins, it's a hell of a lot cheaper (and probably safer) than SAM-e.
>
> KShipping at BAC is $5.00 flat rate for standard shipping, which comes within a week. I've ordered from them several times now and like their service and products.
I have NOW brand B12 and folic acid which I bought in my local health food store. It's probably a bit cheaper at iherb. B12, methylcobalamin was $12.95 for 100 lozenges of 1000 mcg. 1000 mcg is enough per day, I believe. Folic acid is even more inexpensive, $3.95 for 250 tablets of 800 mcg each that also include 25 mcg of cyanocobalamin. Larry said in that previous thread that it's ok to take a little cyanocobalamin type B12 too but the methylcobalamin is the preferred form. There's usually 400 mcg of folic acid in a B complex. Not sure if more is needed or not. Larry told me last year to experiment, see how it felt.
JL
Posted by KaraS on November 14, 2004, at 19:20:12
In reply to Re: TMG/rhodiola » KaraS, posted by JLx on November 14, 2004, at 18:54:55
> > > > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
> > >
> > > Do you know what the monthly cost of this would be?
> > >
> > >
> > > - Scott
> >
> >
> > It's quite a bit cheaper than SAM-e. I need to find Larry's old posts to see about the dosage range of TMG + B12 he recommends so I could give you some accurate figures. You might need to add in folate to balance the B12 as well. SAM-e works for some people in varrying dosages - anywhere from 200-1600 mg. a day - so your cost would vary considerably based on dosage required.
> >
> > I'll do a little searching for those old posts later and get back to you on this (assuming that Larry or someone else doesn't get to it first).
> >
> >
> > K
> >
>
> I see in the long running "Supplements for Brain Fog" thread http://www.dr-bob.org/babble/alter/20040613/msgs/363881.html that you said in July that you were might try TMG and that you were also taking Rhodiola? How did either of those work?
>
> JLYou know in researching the price of TMG for Scott, I ran across some of those old posts of mine and I feel so embarrassed. I just went on and on - drilling poor Larry about every supplement in the world. Desperation was talking. Hopefully people understand. At least there was humor in some of them.
In getting back to your question,
I tried the Rhodiola and it didn't go well at all. It started out ok but ended up making me feel sick and very tired. Similar situation with Perika SJW. They're both thought to be quite dopaminergic. Now that I know about my dopamine autoreceptor problem, I understand my reaction. I haven't tried the TMG yet. I got no response whatsoever to SAM-e even though I was taking 1200 mg. a day so I'm not optimistic about it. Larry thinks it may work for me even though SAM-e didn't so it's still on my list to try.How about you? Have you tried either of them?
Posted by JLx on November 14, 2004, at 19:35:53
In reply to Re: TMG/rhodiola » JLx, posted by KaraS on November 14, 2004, at 19:20:12
> You know in researching the price of TMG for Scott, I ran across some of those old posts of mine and I feel so embarrassed. I just went on and on - drilling poor Larry about every supplement in the world. Desperation was talking. Hopefully people understand. At least there was humor in some of them.No need to be embarrassed,imo. :) I found them interesting.
> In getting back to your question,
> I tried the Rhodiola and it didn't go well at all. It started out ok but ended up making me feel sick and very tired. Similar situation with Perika SJW. They're both thought to be quite dopaminergic. Now that I know about my dopamine autoreceptor problem, I understand my reaction.Interesting. I tried SJW way back when and I didn't think it did anything at all, but it could have been an inferior brand.
>I haven't tried the TMG yet. I got no response whatsoever to SAM-e even though I was taking 1200 mg. a day so I'm not optimistic about it. Larry thinks it may work for me even though SAM-e didn't so it's still on my list to try.
>
> How about you? Have you tried either of them?Yes, I felt good on SAMe, but only when I took 1600mg, I think. The way they figure the dosage was strange, something like you have to take twice what it actually says? I hadn't even remembered that SAMe pooped out for me until I read that old thread where *I* picked Larry's brain at length. ;) I thought I quit taking it when I ran out because it cost so much.
Anyway, I said on there that I felt good taking 800 TMG 3 times a day, but not less. Hadn't remembered taking that much then so recently I've only been taking about 700mg a day. I'm going to increase it tomorrow and see how it feels.
I don't have your dopamine receptor problem though, that I know of. Seems to me like I read something recently that a sensitivity can actually indicate that that's what's needed, so a small dose might have to be built up over time? Does that sound logical? I can't remember where I read it or if it was specifically about dopamine receptors or some other receptors.
At any rate, if you buy the bulk TMG it's not very expensive and you can play around with the amount easily. I buy magnesium malate from BAC, btw. It's quite tolerable to mix with water taste-wise, unlike the very bitter magnesium glycinate which I also get from there. I have amino acids from them too.
JL
Posted by KaraS on November 14, 2004, at 19:36:51
In reply to How much TMG to take? And how 'bout MSM too?, posted by JLx on November 14, 2004, at 18:42:34
> > > > > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
> > > >
> > > > Do you know what the monthly cost of this would be?
> > > >
> > > >
> > > > - Scott
> > >
> > >
> > > It's quite a bit cheaper than SAM-e. I need to find Larry's old posts to see about the dosage range of TMG + B12 he recommends so I could give you some accurate figures. You might need to add in folate to balance the B12 as well. SAM-e works for some people in varrying dosages - anywhere from 200-1600 mg. a day - so your cost would vary considerably based on dosage required.
> > >
> > > I'll do a little searching for those old posts later and get back to you on this (assuming that Larry or someone else doesn't get to it first).
> > >
> > >
> > > K
> > >
> >
> > Here's one thread from a year ago: http://www.dr-bob.org/babble/alter/20031104/msgs/278139.html There's a lot of info in Larry's posts there. DSCH also makes an important note, I think, that it was magnesium that "turned on" TMG for him.
> >
> > TMG is availble through Beyond a Century in bulk form, so inexpensive that way. It's tolerable tasting dissolved in water.
> >
> > JL
>
> I was reading over that old thread...so glad to have this documentation sometimes! I see I was taking about 800 mg of TMG 3 times a day. I didn't realize it was so much and though I have been taking it again lately, not that much. I was feeling loads better in those days too.
>
> I have noticed that taking the TMG feels different since I've been taking MSM, but again maybe I'm not taking enough. What exactly is the relation to TMG and MSM, other than that they are methyl donors? I usually take 1-2,000 mg of MSM, though I've been slacking off lately. Hmm...maybe this is why I feel more crappy.
>
> This board is so helpful. :)
>
> "Research has found that TMG is converted into SAM in the body. TMG is less expensive than SAM.
> Dosage: 3,000 milligrams a day, followed by a maintenance dose of 1,000 milligrams a day for up to three weeks." http://www.holistic-online.com/Remedies/Depression/dep_nutrition2.htm#TMG
>
> I'm reading "Optimum Nutrition for the Mind" and Patrick Holford recommends TMG 600-2000 mg daily on an empty stomach or with fruit.
>
> JL
Oops. I posted my quick summary of TMG cost and dosage before I saw this post. Looks like the lower end of the 1-8 grams is more in line with other recommendations.I hadn't read that you have tried this either before answering your previous post. Sometimes it is hard to discern what is making us feel better or worse. I have been slacking off on taking my supplements as well. I was particularly bad about taking the B's. I had a really rough couple of days recently and I wouldn't be surprised if this had something to do with it. Hard to separate things out and also hard to figure out what is just a normal dip. Bad moods happen to everone. Anyway, I made some big changes as a result and I do feel much better now. Long way to go however but way better than those few days from hell.
Dunno about the MSM. I was taking 1000 mg./day and I didn't seem to notice anything good or bad from it physically or mentally. I have arthritis in one of my fingers and I was taking it mostly for that purpose. Ironically, now that I'm no longer taking the MSM, my finger seems fine. The only difference is that I've added the magnesium to my daily routine. Does that make any sense?
Yeah, this board really is great (as well several other boards on this site). I've learned so much and gotten so much support. Prior to this site and the Internet in general, I was just swinging in the dark.
Kara
Posted by JLx on November 14, 2004, at 19:52:30
In reply to Re: How much TMG to take? And how 'bout MSM too? » JLx, posted by KaraS on November 14, 2004, at 19:36:51
> > > > > > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
> > > > >
> > > > > Do you know what the monthly cost of this would be?
> > > > >
> > > > >
> > > > > - Scott
> > > >
> > > >
> > > > It's quite a bit cheaper than SAM-e. I need to find Larry's old posts to see about the dosage range of TMG + B12 he recommends so I could give you some accurate figures. You might need to add in folate to balance the B12 as well. SAM-e works for some people in varrying dosages - anywhere from 200-1600 mg. a day - so your cost would vary considerably based on dosage required.
> > > >
> > > > I'll do a little searching for those old posts later and get back to you on this (assuming that Larry or someone else doesn't get to it first).
> > > >
> > > >
> > > > K
> > > >
> > >
> > > Here's one thread from a year ago: http://www.dr-bob.org/babble/alter/20031104/msgs/278139.html There's a lot of info in Larry's posts there. DSCH also makes an important note, I think, that it was magnesium that "turned on" TMG for him.
> > >
> > > TMG is availble through Beyond a Century in bulk form, so inexpensive that way. It's tolerable tasting dissolved in water.
> > >
> > > JL
> >
> > I was reading over that old thread...so glad to have this documentation sometimes! I see I was taking about 800 mg of TMG 3 times a day. I didn't realize it was so much and though I have been taking it again lately, not that much. I was feeling loads better in those days too.
> >
> > I have noticed that taking the TMG feels different since I've been taking MSM, but again maybe I'm not taking enough. What exactly is the relation to TMG and MSM, other than that they are methyl donors? I usually take 1-2,000 mg of MSM, though I've been slacking off lately. Hmm...maybe this is why I feel more crappy.
> >
> > This board is so helpful. :)
> >
> > "Research has found that TMG is converted into SAM in the body. TMG is less expensive than SAM.
> > Dosage: 3,000 milligrams a day, followed by a maintenance dose of 1,000 milligrams a day for up to three weeks." http://www.holistic-online.com/Remedies/Depression/dep_nutrition2.htm#TMG
> >
> > I'm reading "Optimum Nutrition for the Mind" and Patrick Holford recommends TMG 600-2000 mg daily on an empty stomach or with fruit.
> >
> > JL
>
>
> Oops. I posted my quick summary of TMG cost and dosage before I saw this post. Looks like the lower end of the 1-8 grams is more in line with other recommendations.
>
> I hadn't read that you have tried this either before answering your previous post. Sometimes it is hard to discern what is making us feel better or worse. I have been slacking off on taking my supplements as well. I was particularly bad about taking the B's. I had a really rough couple of days recently and I wouldn't be surprised if this had something to do with it. Hard to separate things out and also hard to figure out what is just a normal dip. Bad moods happen to everone. Anyway, I made some big changes as a result and I do feel much better now. Long way to go however but way better than those few days from hell.
>
> Dunno about the MSM. I was taking 1000 mg./day and I didn't seem to notice anything good or bad from it physically or mentally. I have arthritis in one of my fingers and I was taking it mostly for that purpose. Ironically, now that I'm no longer taking the MSM, my finger seems fine. The only difference is that I've added the magnesium to my daily routine. Does that make any sense?
>
> Yeah, this board really is great (as well several other boards on this site). I've learned so much and gotten so much support. Prior to this site and the Internet in general, I was just swinging in the dark.
>
> KaraI started taking MSM after my geriatric dog did so well on a glucosamine/chondroitin/MSM formula. I have aches and pains and had osteoarthritis in my back per x-ray way back nearly 20 years ago so I can only imagine what it might look like now. Glucosamine is actually supposed to prevent further degradation in joints, so I wish I were more diligent about taking it. Sometimes I just get sick of taking all this stuff, especially when I'm eating irregularly as I've been -- unless I can see a definite benefit like I do with magnesium. MSM seemed to help my mood, which is an indication of being undermethylated I suppose. I think the TMG may be more powerful though for that.
I think the magnesium could be helping your finger. It generally is relaxing and also opens capillaries. Perhaps you're getting more blood flow.
Yes, it's hard to discern "normal" bad moods from effects of supplements or other anti-depressant efforts like exercise. It's usually in hindsight where I think, "Oh, yeah, I guess that was helping more than I thought at the time".
I did feel better last fall than I do this year so now that I know I was taking a lot more TMG then, I'm going to do that again and hope for the best.
Holistic online, says: SAM is involved in the methylation of monoamines, neurotransmitters, and phospholipids such as phosphatidylcholine and phosphatidylserine. http://www.holistic-online.com/Remedies/Depression/dep_nutrition2.htm
Maybe, since it works more generally like that rather than just boosting one thing, TMG will work for you as Larry suggested.
JL
Posted by tealady on November 14, 2004, at 20:02:55
In reply to Re: SAMe augmentation for resistant MDD, posted by JLx on November 14, 2004, at 17:59:24
In your post you linked to http://www.dr-bob.org/babble/alter/20031104/msgs/278139.html
you mention
On the Alternative Mental Health site, in comments by Dr. Walsh of the Pfeiffer Clinic, http://www.alternativementalhealth.com/articles/walshQZ.htm#Ta, he says for the under-methylated (as I think I am, due to my positive response to SAMe in the past),"Treatment focuses on the use of ANTIFOLATES such as calcium, methionine, SAMe, magnesium, zinc, TMG, omega-3 essential oils, B6, inositol, and A, C and E. The dose of inositol is 500 to 1000mg. Choline is anti-dopaminergic and often makes undermethylated patients worse. Also bad are DMAE, copper and FOLIC ACID"
OK..so what was your repsonse to SAMe in the past that made you think you were undermethylated (that sounds like you've run out of the metho:)
Ane even more importantly what's this about FOLIC ACID and DMAE as well as choline making patients worse..
Did you ever get an answer on those? Caus I felt worse on choline and DMAE I suspect (last week)..and folic acid in itself did, at best, NOTHING for me.
..and I react strange to B12 too..
I'm trying to work out a good combo to order in from the US...with things like
TMG,
NAC,
P5P Now brand with the magnesium,
Coenzymated B's (just in case for B2, B12)Now what else are MUST HAVES to complete the group for optimal balance?
I do have some glucosamine sulfate chondritin sulfate, MSM powder combo bought last week..it does have a load of sugar in it...they all did.
if I have to get SAMe..I think it will have to be from the US..over here its about $90AUD for 60 tablets of 200mg (on special).. way dearer than CoQ10.
Jan
Posted by JLx on November 14, 2004, at 21:23:10
In reply to Re: SAMe , methylation etc » JLx, posted by tealady on November 14, 2004, at 20:02:55
> In your post you linked to http://www.dr-bob.org/babble/alter/20031104/msgs/278139.html
> you mention
> On the Alternative Mental Health site, in comments by Dr. Walsh of the Pfeiffer Clinic, http://www.alternativementalhealth.com/articles/walshQZ.htm#Ta, he says for the under-methylated (as I think I am, due to my positive response to SAMe in the past),
>
> "Treatment focuses on the use of ANTIFOLATES such as calcium, methionine, SAMe, magnesium, zinc, TMG, omega-3 essential oils, B6, inositol, and A, C and E. The dose of inositol is 500 to 1000mg. Choline is anti-dopaminergic and often makes undermethylated patients worse. Also bad are DMAE, copper and FOLIC ACID"
>
>
> OK..so what was your repsonse to SAMe in the past that made you think you were undermethylated (that sounds like you've run out of the metho:)Just that I *did* respond to SAMe which indicates undermethylation.
> Ane even more importantly what's this about FOLIC ACID and DMAE as well as choline making patients worse..
This was Larry's response to that post. http://www.dr-bob.org/babble/alter/20031104/msgs/278173.html Between that and what he said later, I took it to mean that he thought Pfeiffer was wrong, but to experiment oneself with folate to be sure.
> Did you ever get an answer on those? Caus I felt worse on choline and DMAE I suspect (last week)..and folic acid in itself did, at best, NOTHING for me.
> ..and I react strange to B12 too..Well, the subsequent discussion on choline and DMAE was inconclusive. I still haven't determined if lecithin is helpful or not. Just bought some recently to try it again. I took DMAE years ago and felt terrible on it. But that was in my premagnesium days when I also felt awful from tyrosine.
> I'm trying to work out a good combo to order in from the US...with things like
> TMG,
> NAC,
> P5P Now brand with the magnesium,
> Coenzymated B's (just in case for B2, B12)
>
> Now what else are MUST HAVES to complete the group for optimal balance?I'm not sure.
> I do have some glucosamine sulfate chondritin sulfate, MSM powder combo bought last week..it does have a load of sugar in it...they all did.
>
> if I have to get SAMe..I think it will have to be from the US..over here its about $90AUD for 60 tablets of 200mg (on special).. way dearer than CoQ10.
>
> JanI think I'd just try the TMG then. From what Larry's said, it's less potentially harmful in not increasing homocysteine anyway.
JL
Posted by KaraS on November 14, 2004, at 21:52:59
In reply to Re: TMG dosage and cost - quick summary » KaraS, posted by JLx on November 14, 2004, at 19:18:31
Posted by KaraS on November 19, 2004, at 0:55:07
In reply to How much TMG to take? And how 'bout MSM too?, posted by JLx on November 14, 2004, at 18:42:34
> > > > > You can substitute trimethylglycine plus B12 for the SAMe. They're precursors and some (including Larry) consider this to be a more efficient way to go as well.
> > > >
> > > > Do you know what the monthly cost of this would be?
> > > >
> > > >
> > > > - Scott
> > >
> > >
> > > It's quite a bit cheaper than SAM-e. I need to find Larry's old posts to see about the dosage range of TMG + B12 he recommends so I could give you some accurate figures. You might need to add in folate to balance the B12 as well. SAM-e works for some people in varrying dosages - anywhere from 200-1600 mg. a day - so your cost would vary considerably based on dosage required.
> > >
> > > I'll do a little searching for those old posts later and get back to you on this (assuming that Larry or someone else doesn't get to it first).
> > >
> > >
> > > K
> > >
> >
> > Here's one thread from a year ago: http://www.dr-bob.org/babble/alter/20031104/msgs/278139.html There's a lot of info in Larry's posts there. DSCH also makes an important note, I think, that it was magnesium that "turned on" TMG for him.
> >
> > TMG is availble through Beyond a Century in bulk form, so inexpensive that way. It's tolerable tasting dissolved in water.
> >
> > JL
>
> I was reading over that old thread...so glad to have this documentation sometimes!It's better than keeping a journal. You have your history plus the input from others.
I see I was taking about 800 mg of TMG 3 times a day. I didn't realize it was so much and though I have been taking it again lately, not that much. I was feeling loads better in those days too.
So along with more DHEA, you're going to increase your TMG?
> I have noticed that taking the TMG feels different since I've been taking MSM, but again maybe I'm not taking enough. What exactly is the relation to TMG and MSM, other than that they are methyl donors? I usually take 1-2,000 mg of MSM, though I've been slacking off lately. Hmm...maybe this is why I feel more crappy.
>
> This board is so helpful. :)> "Research has found that TMG is converted into SAM in the body. TMG is less expensive than SAM.
> Dosage: 3,000 milligrams a day, followed by a maintenance dose of 1,000 milligrams a day for up to three weeks." http://www.holistic-online.com/Remedies/Depression/dep_nutrition2.htm#TMGSo you take the 3,000 mg. for how long and then you switch to 1,000 mg. for a maintenance dosage?
Then why do you stop taking it after three more weeks?> I'm reading "Optimum Nutrition for the Mind" and Patrick Holford recommends TMG 600-2000 mg daily on an empty stomach or with fruit.
That's in the same ball park.
-K
Posted by KaraS on November 19, 2004, at 1:05:33
In reply to Re: TMG/rhodiola » KaraS, posted by JLx on November 14, 2004, at 19:35:53
> Yes, I felt good on SAMe, but only when I took 1600mg, I think.
Interesting. I think I already mentioned that I got up to 1200 mg. a day and felt nothing so I gave up. I figured that I should have felt something by then. Maybe I should have gone up to 1600. I found it very hard to do though because you're not supposed to take more than 400 mg. at a time and you have to take it an hour before you eat and 2 hours after you've eaten. How do you manage to do that 4 times a day? I felt like my entire life was revolving around taking the SAM-e.
The way they figure the dosage was strange, something like you have to take twice what it actually says? I hadn't even remembered that SAMe pooped out for me until I read that old thread where *I* picked Larry's brain at length. ;) I thought I quit taking it when I ran out because it cost so much.So it can poop out too? It's hard enough finding things that work but then they poop out. It's maddening.
> At any rate, if you buy the bulk TMG it's not very expensive and you can play around with the amount easily. I buy magnesium malate from BAC, btw. It's quite tolerable to mix with water taste-wise, unlike the very bitter magnesium glycinate which I also get from there. I have amino acids from them too.
I'm definitely going to order some from them in bulk.
K
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