Could Andrographolide From Andrographis paniculata Help With Multiple Sclerosis?

Results from a 2-year, double-blind, placebo-controlled study

By Bert Mathieson, ND, RD, CDCES

Printer Friendly PagePrinter Friendly Page

Reference

Ciampi E, Uribe-San-Martin R, Cárcamo C, et al. Efficacy of andrographolide in not active progressive multiple sclerosis: A prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial. BMC Neurol. 2020;20(1):1-10.

Study Objective

To determine if a pure andrographolide compound (AP)extracted from Andrographis paniculata could reduce brain atrophy and disability progression in not-active progressive multiple sclerosis

Design

A 24-month-long, double-blind, placebo-controlled, randomized study at a single site in Chile

Intervention

The andrographolide group received 140 mg of andrographolide (99.5% purity) orally twice daily for 24 months. The placebo group received an identical control.

Participants

There were 44 patients (24 women, 20 men) randomized to this study, and 37 (24 women, 13 men) participants who completed the study. Of the 37 participants, 17 were in the placebo group and 20 were in the AP group.

All patients were older than 18 (mean = 58 years old for placebo group and 59 for AP group) and had a diagnosis of not-active, primary or secondary, progressive MS according to the McDonald 2010 criteria. They had no evidence of relapses or new brain lesions in the last year. All patients had a baseline score on the Expanded Disability Status Scale (EDSS) of less than 8.0 and a score on the Mini Mental State Exam (MMSE) of greater than 24.

Exclusionary criteria included patients with relapsing-remitting MS or active (clinical or radiological) progressive MS, the use of glucocorticoids 3 months prior to the study, or immunomodulatory drugs for 6 months prior to study, uncontrolled medical or psychiatric disorders, and pregnancy or inability to use contraception.

Study Parameters Assessed

Clinical disability was assessed every 12 weeks for 96 weeks by a blinded investigator who tracked scores on the EDSS and on the Multiple Sclerosis Functional Composite (MSFC).

A whole-brain MRI was performed at baseline and at 24 months. The thickness of the retinal fiber nerve layer was estimated at baseline and 24 months.

This study assessed changes in disability progression. Various measures were used to quantify this, including:

  • Mean change in the retinal nerve fiber layer thickness measured by optical coherence tomography (OTC)
  • Mean change in a timed 25 foot walk test (T25WT), a 9-hole peg test (9HPT), the Symbol Digit Modalities Test (SDMT), the Fatigue Severity Scale (FSS), the Multiple Sclerosis Impact Scale (MSIS29), and the Beck Depression Inventory (BDI)

Primary Outcome Measures

The primary outcome measure was the difference in the mean percentage brain volume change (mPBVC) measured by MRI at baseline and at 2 years.

Key Findings

Although the primary outcome measure of percentage brain volume change did not reach statistical significance, 2 other secondary outcome measures reached statistical significance. There was a significant reduction in brain atrophy noted in the AP group vs the placebo group (36.5% as measured by SIENA, and 75% post hoc as measure by BPF, P=0.033). The percentage of patients with a 12-week confirmed disability progression also showed a statistically significant decrease in the AP group vs the placebo group (HR=0.596; 95% CI: 0.2000-1.777).

Practice Implications

Andrographis paniculata has traditionally been used to treat inflammation and bacterial infections. The most active component is believed to be andrographolide, a diterpenoid. Andrographolide has been noted to have antiobesity, anticancer, antidiabetic, and anti-inflammatory effects to name but a few.1 Clinically I have observed that persistent Lyme disease and coinfections present as a complex symptom constellation related to unchecked inflammatory pathways. In my practice, tinctures of the aerial parts of Andrograpis paniculata (usually along with other plants) have been a valuable player in the fight against Lyme-induced inflammation. Given my history with this plant it did not surprise me that the presumed active component could improve symptoms and decrease progression in MS.

In my experience there is significant crossover between tickborne diseases and MS. I have seen several patients who were diagnosed with MS who had a significant improvement in their MS symptoms when an underlying tickborne disease was treated. Was the MS made worse by the tickborne disease? Did the tickborne disease cause the MS? Was MS actually a misdiagnosis? It’s anyone’s guess. Regardless, I advise checking your MS patients for tickborne diseases. You may be quite surprised by what you find.

In the context of MS it would be interesting to see if high doses of the whole plant, as a tincture or as a hot water extract, would have similar positive effects to andrographolide

I have been using Andrographis paniculata as a tincture in the treatment of tickborne infections for many years in my practice. I started this at the recommendation of the well-known herbalist Stephen Harold Buhner. Buhner has written extensively on this plant and states that is a good systemic herb that can cross the blood-brain barrier and reach places where bacteria hide.2 I have found these properties to be very important in the case of Lyme disease since the Borellia spirochetes are notorious for hiding in various body spaces.

The authors of the current study stated that AP was well tolerated and was shown to have mild potential side effects (rash and dysgeusia). Clinically this would be a welcome relief given the potential side effects of anti-inflammatory and immune-modulating drugs that are currently being used to treat MS.

The authors of a study in the New England Journal of Medicine reviewed the adverse effects of ocrelizumab (a monoclonal antibody used to treat MS) in a trial known as the OPERA I trial. In this trial 80.1% of the 408 patients noted an adverse event. Serious adverse events were reported in 6.9% of the patients. Some of the serious adverse events included infections and neoplasms.3

In the current study 13% of patients in the AP group and 42.8% of those in the placebo group reported a “severe” adverse event. This was due to more cardiovascular events in the placebo group despite the balanced comorbidities at the start of the study. The adverse events reported consisted of rashes (12/23 in the AP group vs 0/21 in the placebo group) and dysgeusia (3/23 in the AP group vs 0/21 in the placebo group.) So nearly half the AP group got rashes. Evidently the rashes were not bad enough to be reported as “severe” adverse events in most cases. Only one person dropped out of the AP group and that was due to dysgeusia.

In clinical practice if half of the people I treat with a particular therapy develop a rash, that would definitely discourage them from following through with the treatment. That being said, given the current treatment options for MS, perhaps a minor rash is not such a bad side effect to tolerate. In the current study the rashes did not seem to discourage any in the treatment group from continuing the treatment. Fewer people dropped out of the study in the treatment group (13%) than the placebo group (19%).

Buhner noted that there are reports of allergic reactions to AP. In those who experience side effects from this plant, skin reactions are the most commonly seen manifestation. No fatalities have been reported in the literature from allergic reactions to this plant.4 Personally, I have not seen many rashes from the use of AP tincture and I have used it in several hundred patients. Whether this reaction is dose-dependent or other confounders are involved is not clear.

In the context of MS it would be interesting to see if high doses of the whole plant, as a tincture or as a hot water extract, would have similar positive effects to andrographolide since the increased incidence of rashes with pure andrographolide may inhibit some from following through with treatment.

Since there is now interest in pure andrographolide extract there will likely be drug development centered around this phytochemical. Plants are an ever-present source of inspiration for drug development. In the 30 years leading up to 2012 up to 50% of all new drugs were at least partially derived from plant molecules. A few of the plant-derived drugs developed more recently include Artemether from Artemesia anua used to treat malaria, Nitisinone from Callistemon citrinus used to treat tyrosinemia, and Galantamine from Galanthus nivalis used to treat Alzheimer’s disease.5

It is interesting that andrographolide has anticancer and antiinfective properties, whereas Ocrelizumab was noted to increase the risk of cancer and infections in some cases.3

Limitations

The current study was a very small trial. Perhaps future studies will confirm that andrographolide is a useful tool in the treatment of MS. Andrographolide may also end up lowering the risk of cancer and infections in people who use it for the treatment of MS and other conditions. Part of the beauty of botanical medicine is that you can target several biological processes with one plant or plant extract.

About the Author

Bert Mathieson, ND, RD, CDCES, is a naturopathic doctor, registered dietitian, and certified diabetes educator. He is the medical director at New Hampshire Natural Health Clinic in Bedford, New Hampshire. Mathieson is a general family practitioner and has special interests in diabetes, Lyme disease, and cancer. He is a member of the Oncology Association of Naturopathic Physicians (OncANP) and the International Lyme and Associated Diseases Society (ILADS). In his spare time, he enjoys competing internationally in freestyle skateboarding and kayaking with his wife, Kitty.

References

  1. Dai Y, Chen SR, Chai L, Zhao J, Wang Y, Wang Y. Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide. Crit Rev Food Sci Nutr. 2019;59(sup1):S17-S29.
  2. Buhner SH. On the natural healing of Borrelia infections. Healing Lyme: Natural Healing of Lyme Borreliosis and the Coinfections Chlamydia and Spotted Fever Rickettsioses. Silver City, NM: Raven Press: 2015:196.
  3. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376[3]:221-234.
  4. Buhner SH. On the natural healing of Borrelial infections. Healing Lyme: Natural Healing of Lyme Borreliosis and the Coinfections Chlamydia and Spotted Fever Rickettsioses. Silver City, NM: Raven Press: 2015: 369-370.
  5. Veeresham C. Natural products derived from plants as a source of drugs. J Adv Pharm Technol Res. 2012;3(4):200-201.