Updated November 2026 · By Joel Blackstock, LICSW-S

N-acetylcysteine (NAC) is the only supplement with more than a few controlled trials in OCD, and the results of those trials conflict. Inositol, glycine, 5-HTP, milk thistle, Echium, valerian and ashwagandha rest on one to three small trials each. St. John’s wort and fish oil failed their trials. None of them replaces exposure therapy or serotonin medication.

This page makes one argument. The appeal of a natural fix for OCD often draws on the same need that drives the disorder: a clean, certain answer that ends doubt. Supplements cannot give that, and the way people use them can quietly become one more ritual. The treatments with the strongest evidence, exposure and response prevention (ERP) and serotonin reuptake inhibitors, work by a different route, and ERP in particular trains a person to act without certainty. A supplement can sit beside that work, chosen with a prescriber. It should not stand in for it.

What the evidence supports first

OCD is not rare. In the National Comorbidity Survey Replication, a nationally representative survey of US adults, 1.2% met criteria for OCD in the past year and 2.3% at some point in their lives. More than a quarter reported an obsession or compulsion at some point, which is why the diagnosis rests on distress and impairment, not on odd thoughts alone.¹

Two treatments carry most of the evidence. The first is cognitive behavioral therapy built around exposure and response prevention: deliberately approaching the feared thought, object or situation, and then not performing the ritual that usually follows. A 2015 meta-analysis of 37 randomized trials by Lars-Göran Öst and colleagues found very large effects for CBT compared with waiting-list and placebo conditions (effect sizes of 1.31 and 1.33), and CBT outperformed antidepressant medication.² The second is serotonergic medication. A Cochrane review of 17 trials and 3,097 participants found SSRIs more effective than placebo, with patients about 1.8 times as likely to respond.³ A 2016 network meta-analysis in The Lancet Psychiatry, covering 54 trials and 6,652 adults, found that behavioral therapy, cognitive therapy, SSRIs and clomipramine all beat placebo, and concluded that combining therapy with medication is probably more effective than therapy alone, at least in severe OCD.⁴ A 2017 review in JAMA reached the same practical conclusion: CBT, with or without an SSRI, remains the preferred place to start.⁵

These treatments do not finish the job for everyone. As one systematic review puts it, about half of patients keep residual or impairing symptoms despite adequate treatment trials.⁶ Much of the supplement research sits in that gap. Many of the trials below added a supplement to serotonin medication, and several enrolled only people who had not responded to it, which is a very different question from whether a supplement can replace treatment. If you are still early in that process, our page on OCD treatment in Birmingham describes how we work with it.

The most useful single reference here is the 2022 clinician guideline from the World Federation of Societies of Biological Psychiatry and the Canadian Network for Mood and Anxiety Treatments. Its 31-member taskforce graded nutrient-based and herbal products only where there was a meta-analysis or at least two randomized trials. NAC received a weak recommendation for OCD-related disorders. No other nutrient-based supplement had enough evidence for any anxiety-related disorder, and the taskforce advised that where these products are used, they be used as add-ons within standard care.⁷

N-acetylcysteine: the strongest case, and still mixed

NAC is an acetylated form of the amino acid cysteine and a precursor to glutathione, one of the body’s main antioxidants, but its psychiatric effects probably run through glutamate and inflammation as well.⁸ Researchers became interested in it for OCD because preclinical and clinical studies have implicated glutamate dysfunction in the disorder, and NAC appears to adjust glutamate release in subcortical brain regions through the cystine-glutamate antiporter.⁹

The randomized trials disagree. In Isfahan, Iran, Hamid Afshar and colleagues gave NAC or placebo for 12 weeks to 48 adults who had not responded to a serotonin reuptake inhibitor. By the end, 52.6% of the NAC group met the trial’s response threshold, a drop of at least 35% on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), against 15% on placebo.¹⁰ A second Iranian trial, in 44 patients with moderate to severe OCD given fluvoxamine plus NAC or fluvoxamine plus placebo, also favored NAC over 10 weeks.¹¹ Two longer trials elsewhere did not. In São Paulo, 40 adults with treatment-resistant OCD took NAC or placebo for 16 weeks. Both groups improved by a few points, the difference between them was not significant, and the one signal was a larger drop in anxiety with NAC.¹² In Melbourne, Jerome Sarris’s 16-week trial of 44 participants also missed its primary outcome, with a benefit only on the compulsions subscale that had faded by week 16.⁹ A pediatric trial at Yale was stopped at 11 children out of a planned 40 because of poor recruitment, so its positive result carries little weight.¹³

Pooled analyses land on the line. A 2018 systematic review found a mean difference between NAC and placebo across four trials that narrowly missed statistical significance (p = .07).⁶ A 2024 meta-analysis of six randomized trials with 195 adults found a benefit only for courses lasting five to eight weeks (p = .05), none for courses shorter than five weeks or longer than 12, and no difference on the separate obsession and compulsion scores.¹⁴ A 2022 meta-analysis covering OCD and related disorders found that NAC improved overall symptom scores more than placebo but did not raise the rate of treatment response.¹⁵

The data in related conditions are somewhat stronger, and also mixed. In adults with trichotillomania, 56% were much or very much improved on NAC versus 16% on placebo.¹⁶ A similarly designed trial in children found no benefit.¹⁷ In adults with skin-picking disorder, 47% of those who completed NAC were much or very much improved, against 19% on placebo.¹⁸

NAC was generally well tolerated in these studies. Gastrointestinal complaints were the most common problem: abdominal pain was more frequent on NAC in the São Paulo trial, and heartburn in the Melbourne trial.^{6, 9, 12} The honest reading is that NAC is a reasonable add-on to raise with a psychiatrist when OCD has only partly responded to standard treatment, and that any effect is modest. It is not a first-line treatment, and nothing in this literature supports using it on its own.

Inositol, glycine, 5-HTP and fish oil

Inositol is a simple sugar alcohol and a precursor in one of the cell’s second-messenger systems. The enthusiasm for it in OCD comes from a 1996 Israeli crossover trial in which 13 patients had lower Y-BOCS scores during six weeks on 18 grams a day than during six weeks on placebo.¹⁹ The same group then added inositol to ongoing serotonin reuptake inhibitor treatment in 10 patients and found no difference from placebo.²⁰ A 2014 meta-analysis that pooled the OCD, panic and PTSD trials found no significant effect on anxiety or obsessive-compulsive symptoms.²¹ Eighteen grams is a large amount to take every day, the trials were tiny, and the one positive result has not been repeated in a controlled trial.

Glycine acts at the NMDA glutamate receptor, which is why it drew interest. There is one randomized OCD trial, published in 2009, not the “preliminary studies” the earlier version cited. It titrated adults up to 60 grams a day, many participants could not keep taking it because of the taste and nausea, so only 14 of 24 were evaluable, and the result fell just short of significance (p = .053).²² That is too little to guide anyone.

5-Hydroxytryptophan (5-HTP) and L-tryptophan are serotonin precursors. A 2020 Iranian trial randomized 60 patients with moderate to severe OCD to fluoxetine plus 5-HTP or fluoxetine plus placebo for 12 weeks and reported better scores and response rates with 5-HTP.²³ That is one trial, run under medical supervision, of a combination that carries real risk outside a trial. Stacking serotonin precursors on an SSRI, clomipramine or St. John’s wort raises the possibility of serotonin syndrome, a drug reaction that ranges from tremor and diarrhea in mild cases to delirium, rigidity and dangerous fever in severe ones.²⁴ Tryptophan also has a cautionary history: a 1989 outbreak of eosinophilia-myalgia syndrome in the United States was traced to tryptophan from a single manufacturer and to changes in how it was produced.²⁵ This is a combination to raise with your prescriber, not one to try at home.

Omega-3 fatty acids are often suggested for mood. For OCD, the only controlled trial is a 2004 crossover study of 11 patients already on SSRIs who received eicosapentaenoic acid (EPA) and placebo for six weeks each. Scores fell in both phases, and the authors concluded that adjunctive EPA is ineffective against OCD.²⁶ The previous version of this article said this trial “showed promise.” It did not.

Herbal remedies: what the trials actually found

St. John’s wort gives the clearest negative result. Kobak and colleagues randomized 60 adults to St. John’s wort or placebo for 12 weeks. Y-BOCS scores fell by 3.43 points on the herb and 3.60 on placebo, and 17.9% versus 16.7% were rated much or very much improved. The authors wrote that the results fail to support St. John’s wort for OCD.²⁷ An earlier open-label study of 12 people had looked encouraging, and its authors noted that the speed of improvement suggested a placebo response, which is what the later controlled trial points to.²⁸ The earlier version of this page called the evidence “mixed.” The one controlled trial was negative.

Milk thistle (Silybum marianum, whose standardized extract is called silymarin) has one OCD trial. In 2010 Sayyah and colleagues in Ahvaz, Iran, compared it with fluoxetine in 35 adults for eight weeks and found no significant difference between the two.²⁹ With no placebo arm and a small sample, “no different from fluoxetine” cannot tell us whether both worked or whether the trial was too small to separate them. A later placebo-controlled crossover trial in trichotillomania failed its primary outcome.³⁰

The “borage” in the original article was Echium amoenum, a plant in the borage family (Boraginaceae) whose dried petals are used in Iranian folk medicine as a calming tea. It is not the common garden borage, Borago officinalis. A 2009 trial in 44 patients found that an aqueous extract beat placebo at weeks four and six.³¹ A 2025 placebo-controlled trial in 40 patients tested a syrup combining Echium with another herb, Rheum ribes. The groups did not differ significantly at any single assessment, though the authors reported a more favorable trend over time with the syrup.³² Safety is a real concern: Echium petals have been reported to contain four toxic pyrrolizidine alkaloids, experimental studies of liver toxicity have conflicted, and laboratory work has found the extract toxic to a human liver cell line.³³

Valerian has one small OCD trial, in which 31 adults took an extract or placebo for eight weeks. The extract group did better at the end, and the authors reported more sleepiness on valerian.³⁴ The wider anxiety evidence is thin: a Cochrane review found a single eligible trial of valerian for anxiety disorders and judged the evidence insufficient to draw conclusions.³⁵ The earlier version of this page said valerian calms like a benzodiazepine “without the same risk of dependence.” That comparison has not been established. Valerian is better known as a sleep aid, which we cover in our review of natural remedies for insomnia.

Ashwagandha (Withania somnifera) also has one OCD trial. Thirty patients already taking SSRIs received a root extract or placebo for six weeks, and the extract group improved more. The groups did not start in the same place, though. Median baseline Y-BOCS was 26 in the ashwagandha group and 18 in the placebo group, which makes the comparison hard to read.³⁶ The 2022 guideline gave ashwagandha modest support in the treatment of anxiety disorders and did not support rhodiola for mood disorders.⁷ Our article on adaptogenic herbs for stress management covers that broader use. Ashwagandha has also been linked to cases of liver injury with jaundice.³⁷

Curcumin’s OCD evidence comes from rats. In a quinpirole model of compulsive checking, curcumin reduced the checking behavior.³⁸ We found no human OCD trials. Turmeric products have meanwhile been linked to a rising number of liver injury cases in the US Drug-Induced Liver Injury Network, including one death. Three of the seven products tested also contained piperine from black pepper, and the authors suggested the combination may be part of the increase.³⁹

Two reviews put all of this in proportion. Sarris and colleagues’ 2012 systematic review of complementary treatments for OCD found 14 controlled studies; several nutrient and herbal trials were positive, but none had been replicated and most used small samples, which the authors said precludes firm confidence in the effects.⁴⁰ A 2020 review of herbal medicines described the evidence for saffron, milk thistle, Echium, St. John’s wort and ashwagandha as tentative and low quality.⁴¹ One more pattern is worth naming. Four of the small trials on this page, on milk thistle, Echium, valerian and zinc, came from one overlapping group of Iranian researchers.^{29, 31, 34, 42} Independent replication is what this field most lacks.

Vitamins, minerals, the gut and lab testing

Low nutrient levels are a different question from supplements as treatment. A 2021 meta-analysis of case-control studies found lower vitamin B12 and higher homocysteine in people with OCD than in controls, but no significant difference in folate or vitamin D.⁴³ The earlier version of this article implied that folate deficiency was linked to OCD; the pooled data do not show that. An Italian study of 50 outpatients found low vitamin D in all but one of them, with lower levels tracking greater severity, and called for supplementation trials.⁴⁴ We could not find a published randomized trial of vitamin D supplementation for OCD. The practical point is ordinary medicine. A second meta-analysis confirmed the B12 and homocysteine findings, and its authors note that B12 deficiency can itself produce nonspecific psychiatric symptoms.⁴⁵ It shows up on an ordinary blood test, so it is worth ruling out. Our article on biological triggers that standard workups can miss covers that kind of screening.

For minerals there is one small zinc trial: 23 patients taking fluoxetine received zinc or placebo, and the zinc group had lower scores at weeks two and eight.⁴² We found no OCD trials of magnesium or selenium on their own. The one study we found that included them, an open-label pilot in 28 adults with treatment-resistant OCD, combined them with NAC, zinc, L-theanine and an active form of vitamin B6. Scores fell over 20 weeks and 23% of participants met its response criteria, with the best results in people with milder symptoms, but without a placebo group the study cannot separate the formula from time and expectation.⁴⁶ If you are weighing magnesium for sleep or general anxiety, our comparison of magnesium L-threonate and magnesium glycinate explains the difference between the forms.

The gut-brain axis is an active research area, but for OCD the evidence is almost entirely in animals. In house mice, the probiotic Lactobacillus rhamnosus GG blocked drug-induced OCD-like behavior about as well as fluoxetine.⁴⁷ A 2024 review of the microbiome in anxiety disorders, PTSD and OCD called the area promising while noting contradictory findings and open questions about how well animal models translate to people.⁴⁸ We found no published randomized trial of a probiotic for OCD in humans. The original section on digestive enzymes (amylase, bromelain, papain) had no OCD research behind it and has been removed.

The earlier version also recommended specialty testing. Micronutrient panels such as SpectraCell and stool tests such as the GI-MAP are commercial laboratory products, and we found no study showing that test-guided supplementation improves OCD. Urine neurotransmitter tests have a more basic problem. More than 90% of the body’s serotonin is made in the gut,⁴⁹ so a urine reading mostly reflects serotonin produced outside the brain, not activity in the circuits involved in OCD. We would not use these tests to choose an OCD treatment.

Broad-spectrum vitamin and mineral formulas are a separate case. The OCD-specific evidence we could find for them is a single published case: an 18-year-old in New Zealand whose symptoms improved on a micronutrient formula, worsened when it was stopped for eight weeks, and improved again when it was restarted.⁵⁰ That on-off-on design is more informative than an anecdote, and it is still one person. We explain why our clinicians recommend Hardy Nutritionals in a separate article, and our micronutrition page describes how we use it. Taproot receives a small commission on Hardy sales made through our offer code, so weigh our enthusiasm with that in mind.

Interactions and safety

Supplements are not tested the way drugs are. Under the 1994 Dietary Supplement Health and Education Act, they are regulated as a category of food and do not go through the FDA’s premarket testing for safety and effectiveness. Between 2007 and 2016 the FDA flagged 776 supplements containing undeclared drug ingredients, mostly sexual-enhancement, weight-loss and bodybuilding products.⁵¹ The interactions that matter most for someone with OCD:

• St. John’s wort activates the pregnane X receptor and induces the liver enzyme CYP3A4 and the drug transporter P-glycoprotein. It lowers blood levels of drugs including cyclosporine, tacrolimus, warfarin, digoxin, midazolam and indinavir. It has caused breakthrough bleeding and unplanned pregnancies with oral contraceptives, and serotonin syndrome when combined with SSRIs.^{52, 53}
• 5-HTP and tryptophan combined with an SSRI, clomipramine or St. John’s wort add to the risk of serotonin syndrome.²⁴
• Ashwagandha and turmeric or curcumin have both been tied to case series of drug-induced liver injury.^{37, 39}
• Echium amoenum contains pyrrolizidine alkaloids, which raises a liver safety concern.³³
• Milk thistle lowered trough levels of the HIV drug indinavir in a human study.⁵²
• Inositol showed a trend toward more stomach upset than placebo in pooled trials,²¹ and a 1996 letter in the American Journal of Psychiatry raised the question of inositol-induced mania.⁵⁴ Anyone with a history of bipolar disorder should discuss it with a prescriber first.
• Valerian was associated with more sleepiness than placebo in the OCD trial,³⁴ which matters if you drive or take other sedating medication.
• NAC can cause abdominal pain or heartburn.^{9, 12}

Bring the actual bottles to your prescriber or pharmacist. The conversation matters more if you are pregnant or nursing, have liver or kidney disease, or take blood thinners, transplant drugs, HIV medication, hormonal contraception or any psychiatric medication.

What this looks like in therapy

OCD runs on doubt. People with checking compulsions score higher on intolerance of uncertainty than both other OCD patients and non-anxious controls,⁵⁵ and people with OCD seek reassurance more intensely and more carefully than people with panic disorder, and are more likely to reassure themselves.⁵⁶ Supplement research folds easily into that pattern. Reading one more trial, checking one more label, asking one more practitioner whether the dose is right: each brings a few minutes of relief and keeps the cycle going, the way any compulsion does.

There is a cultural layer too. Paul Rozin’s surveys of students and American adults found a substantial preference for natural products, stronger for foods than for medicines. Most people with that preference kept it even when told the natural and synthetic versions work equally well, and a majority kept it even when told the two are chemically identical. He concluded that much of the preference is ideational, a moral or aesthetic judgment, rather than a practical one.⁵⁷ Rozin’s earlier work on “sympathetic magic” described the intuition that things which have touched stay connected, so that juice briefly touched by a sterilized cockroach still feels contaminated.⁵⁸ That is the logic of contamination OCD, and it is also part of why “natural” can feel clean and “pharmaceutical” can feel tainted. Neither feeling is evidence. In depth-psychological terms, the search for a pure remedy can carry the same wish the symptoms carry: to be free of doubt and of the mess of risk.

In practice this shapes how we work with OCD in a few concrete ways:

• We ask about everything you take, including supplements, and coordinate with your prescriber instead of working around them.
• We treat a supplement as one decision, made with a prescriber, with an agreed trial period and a way to judge it, and then left alone. Reopening the question every day is a ritual, not research.
• ERP is the core of the work. Exposures are built from your own fear hierarchy, and response prevention includes the mental rituals: reviewing, researching and reassuring yourself. Michelle Craske’s inhibitory learning model explains why. Exposure works by building new learning that competes with the old fear, and it works better when expectations are violated and safety signals are removed.⁵⁹ A capsule taken “just in case” before an exposure can function as exactly that kind of safety signal.
• That learning is a form of brain change through repeated practice, which we discuss in our article on enhancing neuroplasticity. No supplement shortcuts it.
• Some clients also want to understand what their obsessions are guarding against, and depth or parts-based work can add meaning to recovery. It complements exposure; it does not replace it for the symptoms themselves.

If OCD has only partly responded to treatment, the next step is usually a better-delivered course of ERP and a medication review, and only then a conversation about add-ons such as NAC. If you would like help with either, our OCD treatment page describes how we work, or you can contact us with questions or to set up a first appointment.

References

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