Why Some Probiotics Worsen ME/CFS and Long COVID

Written By Dr. Craig
Close-up of probiotic capsules, relevant to ME/CFS and long COVID gut health

Why Many with ME/CFS, Fibromyalgia, or Long COVID Feel Worse on Probiotics

If you've ever tried probiotics and felt worse—more brain fog, bloating, fatigue, or flushing—you’re not imagining it.

For people with ME/CFS, fibromyalgia, or long COVID, standard probiotics may do more harm than good. Many products contain bacterial strains that produce histamine or D-lactic acid, compounds that can exacerbate symptoms in sensitive individuals. This post unpacks the research behind these reactions and offers guidance on choosing low-histamine, D-lactate–free probiotics that are safer for postviral conditions.

The Problem with “One Size Fits All” Probiotics

Most probiotics are designed for the general population—not for those with immune dysregulation, mast cell activation syndrome (MCAS), or small intestinal bacterial overgrowth (SIBO). In these cases, common probiotic strains may:

  • Trigger histamine overload

  • Contribute to D-lactic acidosis

  • Aggravate autonomic symptoms

  • Worsen gastrointestinal issues

Histamine-Producing Probiotics That Can Trigger MCAS Symptoms

Some probiotic strains contain the enzyme histidine decarboxylase (HDC), which converts histidine to histamine—a pro-inflammatory compound that may worsen MCAS and histamine intolerance.

Top Probiotic Strains That Produce Histamine

  • Lactobacillus casei

  • Lactobacillus bulgaricus

  • Lactobacillus delbrueckii

  • Streptococcus thermophilus

  • Lactobacillus reuteri (strain-dependent)

Not all strains within these species produce histamine. HDC activity is strain-specific and influenced by environmental conditions (Sánchez-Pérez et al., 2022; Leuschner et al., 1998).

D-Lactate Producing Probiotics and Brain Fog in ME/CFS

D-lactic acid is a byproduct of carbohydrate fermentation by certain bacteria. In people with SIBO or dysbiosis, it can accumulate and contribute to systemic symptoms.

Symptoms of D-Lactic Acidosis in Chronic Illness

  • Brain fog

  • Ataxia

  • Slurred speech

  • Fatigue

  • Cognitive “crashes”

Research on D-Lactate in ME/CFS and Fibromyalgia

A 2009 study found elevated levels of D-lactate–producing bacteria (L. acidophilus, S. thermophilus) in ME/CFS patients, linking them to neurocognitive symptoms (Sheedy et al., 2009). Given SIBO’s prevalence in fibromyalgia, similar mechanisms likely apply.

The Gut Microbiome in Long COVID, ME/CFS, and Fibromyalgia

Individuals with ME/CFS, long COVID, or fibromyalgia often share overlapping features:

  • Persistent gut dysbiosis

  • Low-grade inflammation

  • Increased mast cell activity

  • Impaired gut barrier function

How Postviral Dysbiosis Affects Histamine and Immune Health

Postviral illness is increasingly recognized as a condition of immune and microbiome dysregulation. Studies show reduced microbial diversity and an overgrowth of pro-inflammatory bacteria in long COVID and ME/CFS (Liu et al., 2022). Histamine and other microbial metabolites can activate mast cells (Theoharides, 2018), while impaired DAO enzyme activity may reduce the body’s ability to clear histamine (Comas-Basté et al., 2019).

Probiotic Brands to Avoid for Histamine Intolerance or SIBO

These commonly used products contain one or more histamine- or D-lactate–producing strains:

  • Bio-Kult Advanced Multi-Strain – Contains L. casei, L. bulgaricus, and S. thermophilus

  • Renew Life Ultimate Flora 50 Billion – Includes L. acidophilus (D-lactate) and L. casei (histamine)

  • Garden of Life RAW Probiotics – Contains L. casei, L. bulgaricus, L. acidophilus, S. thermophilus

  • Jarrow Formulas Jarro-Dophilus EPS – Includes L. casei and L. helveticus (histamine and D-lactate producers)

  • VSL#3 / Visbiome – Contains multiple strains including L. acidophilus, L. helveticus, and S. thermophilus

  • Pure Encapsulations (PureProbiotic, 50B, G.I.) – Popular in chronic illness communities but includes L. acidophilus, L. casei, and S. thermophilus

Probiotic Safety First

A tailored approach matters. It will save you money and the hassle of reacting poorly to a product. Look for formulas that disclose strains and avoid known triggers.

Low-Histamine Probiotic Strains

  • Bifidobacterium infantis

  • Bifidobacterium breve

  • Bifidobacterium longum

  • Lactobacillus plantarum (L. plantarum 299v may be better tolerated than others.)

  • Lactobacillus rhamnosus GG

Safe and Trusted Probiotic Brands for ME/CFS and Long COVID

These brands have all been shown to be free of strains that are histamine or D-lactate producing.

  • Seed Synbiotic – Clinically shown to not raise histamine levels (Lohner et al., 2022)

  • Smidge Sensitive Probiotic (U.S.) – Free from histamine and D-lactate producers

  • Custom Probiotics D-Lactate Free Formula (U.S.) – Powder-based, tailored for neurological symptoms

  • Seeking Health ProBiota HistaminX (U.S.) – Formulated for histamine intolerance

  • TMC Probiotic (UK – The Naked Pharmacy) – Single-strain L. plantarum LP01

  • HU58 by Microbiome Labs (U.S./UK) – Spore-based Bacillus subtilis, non-fermenting and histamine neutral

Final Thoughts: Probiotics Aren’t Always the First Step

For people with ME/CFS, fibromyalgia, MCAS, or long COVID, negative reactions to probiotics are not uncommon, and they are biologically explainable. That doesn’t mean all probiotics are harmful for sensitive patients. Most products just weren’t made for us.

Instead of broad-spectrum formulas, you may benefit from a low-histamine, D-lactate–free probiotic that’s gentle on your system. Tips for safer use:

  • Even well-tolerated strains like L. plantarum vary by subtype

  • Always choose products with transparent labeling

  • Start with low doses or single strains and monitor symptoms

That said, probiotics aren’t always the place to start. A more sustainable approach often begins with dietary strategies—reducing inflammatory foods, increasing fiber and polyphenols, and nurturing your microbiome naturally. Supplements work best when the groundwork has been laid.

If you’ve struggled with probiotics or don’t know where to begin, my online digestive health course offers a step-by-step framework tailored for ME/CFS, fibromyalgia, and long COVID. Learn more here.

 

References

1.     Lohner V, Koch M, Dohnal G, et al. Circulating histamine is not increased following 4-week supplementation with a synbiotic: A randomized, placebo-controlled trial. Front Nutr. 2022;9:931792. doi:10.3389/fnut.2022.931792

2.     Sheedy JR, Wettenhall REH, Scanlon D, et al. Increased D-lactic acid intestinal bacteria in patients with chronic fatigue syndrome. In Vivo. 2009;23(4):621-628.

3.     Sánchez-Pérez S, Comas-Basté O, Veciana-Nogués MT, Latorre-Moratalla ML, Vidal-Carou MC. Biogenic amines in fermented foods: Safety and quality parameters. Trends Food Sci Technol. 2022;119:270-281. doi:10.1016/j.tifs.2021.11.001

4.     Leuschner RGK, Kandler W. Screening for histamine and tyramine-producing bacteria in cheese. Int J Food Microbiol. 1998;39(1-2):1-10. doi:10.1016/S0168-1605(97)00144-7

5.     Liu Q, Mak JWY, Su Q, Yeoh YK, Lui GCY, Ng SSS. Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome. Cell. 2022;185(24):4601-4623.e23. doi:10.1016/j.cell.2022.11.010

6.     Theoharides TC. Mast cells and inflammation. Biochim Biophys Acta Mol Basis Dis. 2018;1864(4 Pt B):996-1002. doi:10.1016/j.bbadis.2017.11.001

7.     Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla ML, Vidal-Carou MC. Histamine intolerance: The current state of the art. Biomolecules. 2019;9(10):707. doi:10.3390/biom9100707

Dr. Craig www.drCourtneyCraig.com
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