I Fucking Love Science Fucked Up on Supplements for Depression

Just like millions of other people on the internet I fucking love “I Fucking Love Science”. Their Facebook page has over 18 million likes, and much of what shows up is interesting, fascinating, and mostly on the money. Recently however, one post by Jerome Sarris titled “Health Check: five supplements that may help with depression” was way off the mark.

The five supplements listed are:

  1. Omega-3 fatty acids,
  2. SAMe,
  3. St John’s wort,
  4. NAC, and
  5. Zinc

I’m not going into the pros and cons of supplements here, I just want to examine what the research he links to actually says.

1. Omega-3 fatty acids,

Just looking at the studies quoted in the article on Omega-3 fatty acids, the researchers came to very different conclusions than Sarris reported.

Fish consumption and major depression. Joseph R Hibbel. The Lancet, Volume 351, Issue 9110, Page 1213, 18 April 1998.

This correlation between apparent fish consumption and lower annual prevalence of major depression does not show that fish consumption can cause differences in the prevalence of major depression or that eating fish or fish oils are useful in treatment. Various cultural, economic, social, and other factors can confound this simple correlational relation.

Without examining the dated research, the authors don’t seem as enthused as Sarris.

Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Bloch MH, Hannestad J.Mol Psychiatry. 2012 Dec;17(12):1272-82.

Nearly all evidence of omega-3 benefit was removed after adjusting for publication bias using the trim-and-fill method (SMD=0.01, 95% CI: -0.13, 0.15). Secondary analyses suggested a trend toward increased efficacy of omega-3 FAs in trials of lower methodological quality, trials of shorter duration, trials which utilized completers rather than intention-to-treat analysis, and trials in which study participants had greater baseline depression severity. Current published trials suggest a small, non-significant benefit of omega-3 FAs for major depression. Nearly all of the treatment efficacy observed in the published literature may be attributable to publication bias.

Yes, if you only publish positive studies, the results will show what you want. Even with that, the benefit is non-significant. That’s not much of an endorsement.

Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. Sarris J, Mischoulon D, Schweitzer I. J Clin Psychiatry. 2012 Jan;73(1):81-6

The meta-analytic findings provide strong evidence that bipolar depressive symptoms may be improved by adjunctive use of omega-3. The evidence, however, does not support its adjunctive use in attenuating mania.

This analysis seems to show that depressive symptoms of bipolar disorder may be improved, however, the authors note that “studies with smaller sample sizes had larger effect sizes“. This indicates to me that the effects might disappear in entirely in larger sample sizes.

In two out of the three, the article directly contradicted the results described by the authors of the studies.

2. SAMe (S-Adenosylmethionine)

Following the link Sarris uses to identify the compound:

However, many of the studies have examined injectable forms of SAMe, not an oral supplement, and the quality of the studies has varied. One well designed study failed to find any benefit.

Hardly a ringing endorsement.

The other links:

Evidence for S-adenosyl-L-methionine (SAM-e) for the treatment of major depressive disorder. Papakostas GI. J Clin Psychiatry. 2009;70 Suppl 5:18-22.

Less evidence supports the use of oral SAM-e, although some trials have demonstrated its efficacy as well. In addition, there is a paucity of evidence examining whether oral forms of SAM-e can be safe, well tolerated, and efficacious when used as adjunctive treatment for antidepressant nonresponders with MDD. Although preliminary data suggest SAM-e may be useful as an adjunctive therapy to antidepressants, controlled studies are needed to confirm or refute these preliminary findings.

Almost the same wording as the first one.

S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M.
Am J Psychiatry. 2010 Aug;167(8):942-8.

These preliminary results suggest that SAMe can be an effective, well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication.

This study is preliminary and had only 73 participants.

Not looking real good here.

3. St John’s Wort

One study linked:

St John’s wort for major depression. Linde K, Berner MM, Kriston L. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD000448.

The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.

This sounds promising, and at least he reported the results accurately. However, even Sarris’ recommendations is qualified on the issue.

4. NAC (N-acetyl cysteine)

Again a single link.

N-acetyl cysteine for depressive symptoms in bipolar disorder–a double-blind randomized placebo-controlled trial.Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI. Biol Psychiatry. 2008 Sep 15;64(6):468-75.

NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar disorder.

However, like the SAMe study above, there were only 75 participants. Also, as Sarris notes, NAC is not easy to come by.

5. Zinc

One study for zinc.

The efficacy of zinc supplementation in depression: systematic review of randomised controlled trials. Lai J, Moxey A, Nowak G, Vashum K, Bailey K, McEvoy M. J Affect Disord. 2012 Jan;136(1-2):e31-9.

LIMITATIONS: There are limited trials examining the effects of zinc supplementation on depressive symptoms. An overall pooled estimate of effect for all included studies could not be calculated and evidence was difficult to summarise because of substantial heterogeneity.

CONCLUSION: Evidence suggests potential benefits of zinc supplementation as a stand-alone intervention or as an adjunct to conventional antidepressant drug therapy for depression. However, there are methodological limitations in existing studies and so further well-designed, adequately powered research is required.

Again, the authors are not recommending zinc for depression. They are saying the evidence hasn’t been found yet.

Sarris concludes with a caveat to consult your physician, and be wary of the quality of supplements. Definitely good advice, as they are untested and unregulated. However, this paragraph isn’t so accurate.

The studies mentioned here tend to support that “add-on” prescription of a range of nutrients, such as omega-3 fatty acids, SAMe, folic acid, N-acetyl cysteine and zinc, with various medicines, such as antidepressants, have a beneficial effect in improving treatment beyond that of placebo. But again, be sure to seek medical advice before combining any supplements with medications.

As indicated above, in some of the cases, Sarris reported conclusions either directly at odds with the authors’ and in others overstated the evidence. If he had linked to articles that gave positive results (assuming they exist) for these products, it would have been one thing. However, his examples were mostly negative, or at most not very positive towards the supplements.

Depression is too often a fatal disease, and we should not be swayed by products that don’t have much to recommend them. Most certainly, we should be under the care of a health care professional who needs to be aware of all prescription and non-prescription medications as well as any supplements you are taking.

This is a very disappointing post showing up on a respected website. We all can make mistakes based upon research that has been supplanted, but science communicators must make a serious attempt to report research results accurately.

I still love IFL Science and I will continue to follow them on Facebook and Twitter. They just came down a notch in respectability for me.

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