# Turmeric's Hidden Risk: A Word of Caution for Patients with Weakened Immune Systems

Turmeric, a spice long considered harmless and even beneficial, may pose hidden risks for people with weakened immune systems. This review article reports the case of a patient with mild immunodeficiency who developed bronchitis after taking turmeric supplements, and explores how curcumin (the active ingredient in turmeric) may suppress critical immune functions through its effects on dendritic cells. The authors urge caution against unsupervised use of turmeric or curcumin in immunocompromised patients, particularly those with monoclonal gammopathy of undetermined significance (MGUS), a condition that affects up to 6.6% of people over age 80.

# Turmeric's Hidden Risk: A Word of Caution for Patients with Weakened Immune Systems

## Table of Contents

- Key Points
- Background: Why This Research Matters
- A Real-World Case: Turmeric Toxicity in a Mildly Immunocompromised Patient
- Curcumin and the Immune System: What We Know
- The Role of Dendritic Cells in Immune Deficiency
- Curcumin and Dendritic Cells: The Key Link
- Dendritic Cells in Patients with MGUS
- Curcumin and the General Public
- Clinical Implications: What This Means for Patients
- Limitations: What This Study Couldn't Prove
- Recommendations for Patients
- Frequently Asked Questions
- Source Information

## Key Points

- Curcumin suppressed dendritic cell maturation and reduced IL-12 production in research, dampening Th1 immune responses.
- A mildly immunocompromised man developed bronchitis on 1 g turmeric twice daily; 200 mg twice daily was tolerated.
- Patients with weakened immune systems or MGUS should not self-medicate with turmeric or curcumin without medical supervision.
- "Natural" does not mean risk-free; high doses or susceptible individuals may experience significant toxicity.

## Background: Why This Research Matters

Curcumin, the major yellow pigment extracted from turmeric, has been rediscovered by modern science as a substance with great promise as a therapeutic agent. It is currently being tested in human clinical trials for a variety of serious conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis, and Alzheimer's disease.

Recently, pilot studies by Golombick and Diamond (2008) and Golombick et al (2009) reported that curcumin, in some patients with monoclonal gammopathy of undetermined significance (MGUS), decreases the paraprotein load (the abnormal protein level in the blood) and the urinary N-telopeptide of type 1 collagen bone turnover marker. These results generated considerable excitement in the medical community.

MGUS is a condition in which a monoclonal (M-) protein is present in the blood without evidence of multiple myeloma, Waldenström's macroglobulinemia, primary amyloidosis, or related disorders. An increasing paraprotein concentration is a known risk factor for the malignant progression of these diseases.

The numbers are significant. The incidence of MGUS increases with age, with prevalence rising from 1.7% in individuals between 50 and 59 years to 6.6% in those above 80 years of age. The average risk of malignant progression for an individual with MGUS is approximately 1.5% per year. MGUS is a serious condition because it leads to an increased risk of mortality, not only due to malignant transformation, but also due to coexisting clinical conditions.

That said, many patients with MGUS never develop symptoms and eventually die of unrelated causes. As a consequence, the medical profession has been very cautious with treatment in MGUS. To date, only regular observation ("watchful waiting") with no treatment is recommended for these patients. This is based on the fear that treatment with, for example, alkylating agents may induce secondary leukemia. Curcumin is believed not to pose this risk, which makes it an attractive candidate for prevention trials.

In a commentary on the Golombick study, Dr. Rajkumar emphasized the crucial importance of developing new methods to prevent the malignant progression of MGUS. Since MGUS often presents no symptoms while progression leads to incurable disease, researchers have been actively looking for agents that could safely delay or prevent progression. Curcumin was proposed as a potential agent for further trials, especially in cases at the highest risk of progression.

The authors of this review find the first results with curcumin in MGUS very encouraging and agree that further trials are warranted. However, they feel the need to express a word of caution based on a case in which the use of moderate doses of turmeric induced some toxicity, possibly related to immunosuppression. The phenomenon was reproducible in their patient and can be understood on the basis of the scientific literature.

## A Real-World Case: Turmeric Toxicity in a Mildly Immunocompromised Patient

The authors describe a 57-year-old male patient with mild hypogammaglobulinemia (low levels of antibodies in the blood) and a subnormal level of IgG caused by an IgG1 subclass deficiency. His laboratory values were carefully documented and compared to normal ranges:

- Total gammaglobulins: 7.91 g/l (normal range: 8.00–13.50)
- Total IgG: 7.18 g/l (normal range: 7.51–15.60)
- IgG1: 3.92 g/l (normal range: 4.90–11.40) — **below normal**

- IgG2: 2.29 g/l (normal range: 1.50–6.40)
- IgG3: 0.43 g/l (normal range: 0.20–1.10)
- IgG4: 0.13 g/l (normal range: 0.08–1.40)

Since early childhood, the patient had suffered from otitis media (middle ear infections), chronic rhinosinusitis, and occasionally bronchitis. The immune disorder also affected other family members, sometimes combined with IgG3 deficiency. Throughout his life, he developed onychomycosis (fungal nail infections), plantar warts, and flat warts that were rather resistant to treatment.

The patient had no history of allergies. Chronic constipation in early life was followed by post-infectious irritable bowel syndrome (IBS) from the age of 25 years. Prior treatment with salazopyrine had not improved the situation, and antibiotic treatment only had a temporary effect.

Encouraged by the pilot study by Holt et al (2005) on curcumin in inflammatory bowel disease, the patient asked to try turmeric for his intestinal problems. His doctors proposed a dose of 1 gram of turmeric (as a food component), two times per day. For context, Holt et al had prescribed 1–1.5 g/day of 99.5% pure curcumin.

The patient confirmed positive results: within weeks, his intestinal complaints became significantly milder, and he experienced a subjective improvement in quality of life. Positive results of curcumin for HIV-associated diarrhea were also described in the literature, further supporting its utility for bowel pathology even in severely immunocompromised patients.

**The critical event:** Within 6 weeks of starting turmeric, the patient developed mild bronchitis with chronic cough and wheezing. This was surprising because traditional Indian medicine actually recommends turmeric for a number of health problems, including sinusitis. The turmeric was discontinued, and the bronchitis cleared completely.

Several weeks later, the patient re-started turmeric. Within 4 weeks, the first signs of wheezing and bronchitis returned. Turmeric was again discontinued for 3 weeks, then resumed at a lower dose of 200 mg two times per day. At this reduced dose, no wheezing or bronchitis developed, and the turmeric was still sufficient to significantly improve his intestinal problems. The patient has now used this lower-dose treatment intermittently for almost 2 years with satisfaction and no toxicity.

The patient has a proven weak and transient response to protein vaccines, and suffers from chronic rhinosinusitis and gastrointestinal problems. Statistics from the medical literature show that **one in two patients with IgG1 deficiency develops ear, nose, throat, and bronchial problems**, while **one in five develops gastrointestinal problems**. The condition is therefore difficult to distinguish from a mild form of common variable immunodeficiency (CVID).

Interestingly, the patient's long-standing plantar warts—which had resisted cryotherapy, X-ray irradiation, topical fluorouracil, and transfer factor injections—spontaneously cleared after he took multivitamin tablets for several months at doses sometimes exceeding the recommended dietary allowance. A recent study in which CVID was defined as a reduction in serum IgG below 7 g/l, recurrent bacterial airway infections, and poor response to vaccinations, found a vitamin B6 deficiency in one out of three patients. Vitamin B6 supplementation resulted in a significant increase in CD4+ T cells in these patients, while the concentration of serum immunoglobulins remained unchanged. Indeed, spontaneous resolution of plantar warts has been associated with an increase in CD4+ T cells.

CVID is a heterogeneous group of disorders characterized by hypogammaglobulinemia and a number of T cell defects that may be primary or secondary. In some patients, apparently including the patient described here, cellular immunity can be improved by vitamin B6 supplementation. The authors speculate that the vitamin B6 deficiency may be related to the gastrointestinal problems known to exist in a subgroup of patients with selective IgG1 deficiency.

## Curcumin and the Immune System: What We Know

A study in Wistar rats demonstrated that prolonged intraperitoneal curcumin injections did not impair the cytotoxic function of natural killer cells. Moreover, the generation of reactive oxygen species and nitric oxide from macrophages, and levels of Th1 regulatory cytokines, remained unaltered. The study concluded that curcumin is a safe pharmacological molecule for immune cells in vivo.

However, the effect of curcumin on dendritic cells (DCs) was not investigated in that study. This is an important gap, because dendritic cells are critical for generating an immune response. After dendritic cells are activated, they mature and migrate to the lymphoid tissue, where they prime T lymphocytes and stimulate a specific or adaptive immune response. This process is foundational to how the body defends itself against pathogens and tumors.

## The Role of Dendritic Cells in Immune Deficiency

Dendritic cells play a key role in mucosal viral infections. Infection with respiratory viruses mobilizes immune cells, including both myeloid (m) and plasmacytoid (p) dendritic cells, to the site of viral entry and promotes their replication in the respiratory tract. The increased number of pDCs in the nasal compartment significantly correlates with viral load, and is associated with a decrease in the number of pDCs in the blood. High numbers of both DC subsets are found in respiratory secretions weeks after the acute symptoms of the viral infection have resolved.

In patients with common variable immunodeficiency (CVID), the differentiation, maturation, and function of dendritic cells are severely perturbed. Key findings from research in this area include:

- DCs in CVID patients produce significantly lower amounts of interleukin-12 (IL-12) upon CD40 signaling compared to controls
- The expression of maturation markers, including CD40, on CVID patient DCs is significantly lower than that of DCs from healthy donors
- Despite heterogeneous clinical presentation, CVID is generally associated with defective DC functions
- Experiments with neutralizing anti-IL-10 monoclonal antibodies indicate that IL-10 may not be the only factor responsible for defective differentiation
- Deficient IL-12 production by DCs is closely correlated with lymphocyte functions in vitro and with absolute numbers of CD4 T cells in peripheral blood
- Although DCs in CVID patients appear morphologically similar to DCs in normal subjects, the lack of IL-12 production and defective antigen presentation demonstrate significant functional defects
- CD40 ligand expression on stimulated T-helper lymphocytes in CVID patients is similar to that in normal controls

These results, along with a more recent study on selective deficits in blood dendritic cell subsets in CVID, point to an important role of defective differentiation and functioning of DCs in the pathogenesis of immunodeficiency in CVID.

## Curcumin and Dendritic Cells: The Key Link

Almost 5 years before this review was published, researchers demonstrated that curcumin is a potent inhibitor of myeloid dendritic cell maturation in mice. In vivo data showed that although curcumin-treated DCs migrated to T cell areas of secondary lymphoid tissue, they failed to induce normal cell-mediated contact hypersensitivity. Reduced IL-12 production observed after curcumin treatment indicated that curcumin induces the immature state of DCs.

Most of the effects of curcumin on the T cell-differentiating properties of DCs were found to be the consequence of the inhibition of IL-12 production. Curcumin-treated DCs failed to induce a normal cell-mediated immune response. The authors of that study proposed that curcumin could be used for inhibiting Th1 responses for therapeutic purposes—for example, in inflammatory conditions like arthritis.

**The double-edged sword:** The activation of the Th1 response plays a pivotal role in the induction of inflammation, such as in arthritis. On the other hand, **Th1 cells are protective against invading pathogens and tumors**. In other words, the anti-inflammatory effect obtained upon treatment of DCs with curcumin comes with an immunosuppressive effect at the same time.

A more recent study investigating the effects of curcumin on human DCs found that curcumin prevented dendritic cells from responding to immunostimulants. Specifically:

- DC-induced CD4+ T cell proliferation was prevented
- Maturation markers were blocked
- The expression of cytokines and chemokines was inhibited
- Migration was also reduced

The authors of that study concluded that curcumin dampens the Th1 response while promoting a Th2-permissive environment. They speculated that curcumin may be disrupting the antigen handling and presenting machinery of dendritic cells, and suggested a potential therapeutic role for curcumin as an anti-inflammatory and immune suppressant.

Since a Th1 pattern of cytokine secretion—in which DC-derived IL-12 plays an essential role—has been associated with protective antitumor responses, dampening the Th1 response by curcumin could be counterproductive in attempts to prevent malignant progression, at least in patients in whom dendritic cell maturation would be compromised.

## Dendritic Cells in Patients with MGUS

In patients with MGUS and multiple myeloma (MM)—which can result from malignant progression of MGUS—significant abnormalities have been demonstrated in the distribution, phenotype, and pattern of secretion of inflammatory cytokines by different subsets of dendritic cells from peripheral blood.

Key finding: Despite reduced secretion of the inflammatory cytokines IL-1, IL-6, IL-8, and TNF in both MGUS and MM patients, the production of IL-12 after short-term in vitro culture was similar in patients with MGUS and controls. Whether curcumin inhibits IL-12 production from dendritic cells in MGUS patients is a critical issue, especially given that immunosuppression is a known risk factor for the development of MGUS.

Studies of familial clusters of Waldenström's macroglobulinemia—another lymphoproliferative disease often preceded by MGUS—have found an increased frequency of IgM MGUS compared to the general population, and have provided data suggesting that the phenotypic spectrum may also include hypoglobulinemia (low antibody levels).

It is conceivable that immunosuppression by curcumin is only relevant in already immunocompromised patients with aberrantly functioning dendritic cells, and not in healthy controls. In subgroups of MGUS patients, the non-affected immunoglobulins are reduced, and these patients show, on average, a higher risk of progression. Whether curcumin perturbs dendritic cell maturation and IL-12 production in these patients—and whether this leads to immunosuppression and increased risk of progression of MGUS—are issues that must be addressed in future clinical trials.

## Curcumin and the General Public

We live in a developing "information society" in which findings reported in the scientific literature—or at least parts of them—are rapidly divulged to the general public. Moreover, companies now include "natural substances" in their products for the health and cosmetic markets. Over the last few years, for example, the benefits of polyphenols have been presented in advertising campaigns for health, diet, and beauty products, and the results of scientific studies have been used and quoted in this context.

This practice could be positive, were it not that the increased public awareness concerning natural products has not countered the relatively widespread misconceptions regarding their toxicity. "Natural" products are considered to pose no or only a minimal toxicity risk. In fact, natural products can—and do—induce significant toxicity when used by susceptible individuals, or when the dose is higher than that normally consumed at dietary levels.

Since turmeric has been used for centuries, it is improbable that problems will arise in healthy individuals when curcumin is ingested at or around the quantities normally found in the diet. However, at significantly higher doses and/or in susceptible individuals, toxicity may occur. For example, the first case of complete atrioventricular block (a serious heart rhythm disturbance) associated with turmeric intake was described and published online in November 2009.

For context on typical exposures: average intake in the adult Indian population is estimated at 2 g/day of turmeric (containing up to 200 mg of curcumin). Phase I clinical trials indicate that even doses of up to 8 g/day of extracted curcumin (diferuloylmethane) provoke only minimal toxicity in healthy volunteers. As a consequence, curcumin is generally believed not to be a risk factor for the induction of secondary leukemia—a concern that exists with some conventional treatments.

## Clinical Implications: What This Means for Patients

The results with curcumin in MGUS are promising, and the authors agree that further trials aimed at delaying progression in MGUS are warranted. However, the case presented here and the literature review suggest a word of caution is needed.

The key concern is that curcumin's immunosuppressive effects—particularly through inhibition of IL-12 production in dendritic cells and dampening of the Th1 response—could be harmful in immunocompromised patients. This is especially relevant for MGUS patients because:

- MGUS itself is associated with immune abnormalities
- Subgroups of MGUS patients have reduced non-affected immunoglobulins, which puts them at higher average risk of progression
- Immunosuppression is a known risk factor for both the development and the progression of MGUS
- Turmeric is easily available as a food component in Asia, the Americas, and Europe, which may lead to unsupervised intake without medical monitoring

**Patients with MGUS, in whom the levels of non-affected immunoglobulins are reduced, should be carefully monitored for toxicity when curcumin is administered.** The authors also note in their acknowledgements that they expressed their concern in a letter to the editor of Clinical Cancer Research.

## Limitations: What This Study Couldn't Prove

The authors are careful to acknowledge that one case does not provide proof of turmeric toxicity. It cannot be ruled out that the patient may have been more susceptible to turmeric toxicity than other patients due to his mildly compromised immune system and/or the related tendency to develop vitamin B6 deficiency.

This is a review article, not a controlled clinical trial. The literature cited includes animal studies (Wistar rats), in vitro studies on mouse and human cells, and pilot studies with small numbers of patients. The exact mechanism by which curcumin might trigger bronchitis—or whether it does so at all in the broader population—remains unclear and requires further investigation.

The development of bronchitis after the use of turmeric or curcumin has, to the best of the authors' knowledge, never been reported elsewhere in the literature. Scientific knowledge is currently insufficient for identifying all risk factors or risk groups; their identification will be the result of planned trials.

## Recommendations for Patients

Based on this review, the authors make several practical points for patients and healthcare professionals:

1.
**Do not self-medicate with turmeric or curcumin without medical supervision**, especially if you have a weakened immune system, MGUS, or a known immunoglobulin deficiency.
1.
**MGUS patients should be carefully monitored for toxicity** when curcumin is administered, particularly those with reduced non-affected immunoglobulins.
1.
**Be aware that "natural" does not mean risk-free.** Natural products can induce significant toxicity when used by susceptible individuals or at doses higher than those normally consumed in the diet.
1.
**Pay attention to dose.** The patient in this case developed bronchitis at 1 gram of turmeric twice daily, but tolerated 200 mg twice daily without respiratory symptoms—a five-fold difference in dose.
1.
**Watch for warning signs.** If you develop respiratory symptoms (cough, wheezing, bronchitis) after starting turmeric or curcumin supplements, discuss this with your doctor.
1.
**Healthcare professionals should inform patients** about the existence of such risks, particularly in the context of increasing public use of "natural" supplements.

## Frequently Asked Questions

### What is MGUS and how common is it?

MGUS, or monoclonal gammopathy of undetermined significance, means a monoclonal protein is present in the blood without evidence of multiple myeloma or related disorders. The prevalence increases with age: 1.7% in people ages 50–59 and 6.6% in those over 80. The average risk of malignant progression is about 1.5% per year.

### Can turmeric or curcumin be harmful for people with weakened immune systems?

Yes, the article reports a case of a mildly immunocompromised patient who developed bronchitis after taking 1 gram of turmeric twice daily. The authors caution against unsupervised use of turmeric or curcumin in immunocompromised patients, especially those with MGUS, because curcumin may suppress critical immune functions through effects on dendritic cells.

### What happened to the patient in the case report?

A 57-year-old man with mild hypogammaglobulinemia and IgG1 subclass deficiency took turmeric for intestinal problems. Within 6 weeks he developed mild bronchitis with cough and wheezing. Stopping turmeric cleared the symptoms. Restarting it brought back bronchitis within 4 weeks. A lower dose of 200 mg twice daily caused no respiratory symptoms and still helped his gut problems.

### How does curcumin affect dendritic cells and the immune system?

Research showed curcumin is a potent inhibitor of myeloid dendritic cell maturation in mice. It reduced IL-12 production, inducing an immature state in dendritic cells. This dampens the Th1 immune response. While this anti-inflammatory effect might help conditions like arthritis, it also means an immunosuppressive effect, which could be counterproductive for protecting against infections and tumors.

### What dose of turmeric caused toxicity in the patient?

The patient developed bronchitis at 1 gram of turmeric taken twice daily. This equals 2 grams of turmeric per day. When he reduced the dose to 200 mg twice daily, he did not develop wheezing or bronchitis, and the lower dose still significantly improved his intestinal problems. The article notes a five-fold difference between the toxic and tolerated dose.

### Should I stop taking turmeric if I have MGUS or a weakened immune system?

The article advises not to self-medicate with turmeric or curcumin without medical supervision, especially if you have a weakened immune system, MGUS, or a known immunoglobulin deficiency. MGUS patients should be carefully monitored for toxicity when taking curcumin, particularly those with reduced non-affected immunoglobulins. Discuss any respiratory symptoms like cough or wheezing with your doctor.

### Are natural products like turmeric always safe?

No. The article says natural products can induce significant toxicity when used by susceptible individuals or in doses higher than normally consumed in the diet. Although turmeric has been used for centuries, higher doses may cause problems in vulnerable people. For example, a case of complete atrioventricular block associated with turmeric intake was reported. Always treat natural supplements with caution.

### Should I get a second opinion before taking turmeric or curcumin if I have MGUS or a weakened immune system?

Yes. Curcumin can suppress immune function by inhibiting dendritic-cell maturation and IL-12 production, which dampens the Th1 response. In a patient with mild immunodeficiency, 1 gram of turmeric twice daily triggered bronchitis; symptoms resolved on discontinuation and recurred on rechallenge. A lower dose of 200 mg twice daily was tolerated. Patients with MGUS or reduced immunoglobulins should be carefully monitored for toxicity if curcumin is administered. A second opinion can help to weigh risks and follow-up plans. Diagnostic Detectives Network provides independent expert second opinions.

## Source Information

**Original article title:** EXPERIMENTAL AND THERAPEUTIC MEDICINE 1: 265-269, 2010

**Authors:** A.J.M. Vermorken, J. Zhu, W.J.M. Van de Ven, Y. Cui, and J.P. Fryns

**Journal:** Experimental and Therapeutic Medicine 1: 265–269, 2010

**DOI:** 10.3892/etm_00000041

**Received:** December 16, 2009; **Accepted:** January 19, 2010

**Key words:** monoclonal gammopathy of undetermined significance, dendritic cells, common variable immunodeficiency, curcumin, information society

**Funding:** This study was supported by a grant from Fonds Wetenschappelijk Onderzoek Vlaanderen (G.0239.07N).

This patient-friendly article is based on peer-reviewed research.


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