Benefits
Upper respiratory symptom scores
In a double-blind trial in 223 people with an uncomplicated upper respiratory infection, 200 mg a day lowered self-rated symptom scores more than placebo by day 5, with every symptom except earache improving more, although scores did not differ on days 1 and 3. Five of the authors worked for the maker.
Respiratory symptom survey scores in a 7-day trial
In a phase III trial in 300 people with a common cold, 200 or 400 mg a day for 7 days gave lower scores than placebo on the trial's main measure, the WURSS-21 symptom survey, on day 3 but not on days 5 or 7. Nasal mucus weight, tissue use and a nasal inflammation marker leaned toward the extract without reaching significance. The abstract does not name the sponsor.
Immune cell and cytokine markers in healthy adults
In a maker-funded study without a placebo group, 30 healthy adults took 200 mg a day for 30 days. Natural killer cell counts, the main outcome, did not change, while interferon gamma and IL-4 rose and IL-2 fell from baseline. These are blood markers, not evidence of fewer or shorter illnesses.
Standardized andrographolide content
The maker states that KalmCold is standardized to more than 30% andrographolide plus six other marker compounds, intended to give a consistent amount from batch to batch. No study has compared it head to head with other andrographis extracts, so standardization alone does not show better results.
Mechanism of action
Inflammatory mediators in cell studies
In cell studies by the maker's laboratory, an extract of Andrographis paniculata leaves lowered nitric oxide, prostaglandin E2, IL-1 beta, IL-6, thromboxane B2 and leukotriene B4 release, but not histamine release. These are lab findings; the cited human trials did not show a matching change in inflammation.
Several active compounds, not only andrographolide
In the same laboratory, purified andrographis compounds differed in activity: andrographolide, isoandrographolide, 7-O-methylwogonin and skullcapflavone I each reduced some inflammatory mediators in cells, and only 7-O-methylwogonin reduced histamine release. This is cell-based work, not evidence of an effect in people.
Clinical trials
Randomized, double-blind, placebo-controlled trial; KalmCold 200 mg a day or placebo, with nine self-rated symptoms scored on a visual analogue scale on days 1, 3 and 5; five co-authors were from the Natural Remedies research center; funding is not stated in the abstract and no registry number is given (Saxena et al. 2010, Phytomedicine)
223 people of both sexes with an uncomplicated upper respiratory tract infection.
Symptom scores did not differ between groups on days 1 and 3. By day 5, every symptom except earache had improved more with KalmCold than with placebo, and overall symptom scores were significantly lower. Minor side effects occurred in 6 of 112 people on KalmCold and 3 of 110 on placebo, a difference that was not significant. The trial used subjective symptom scores only.
Phase III, randomized, double-blind, parallel-group, placebo-controlled trial; AP-Bio 200 mg a day, 400 mg a day or placebo for 7 days (1:1:1); primary outcome WURSS-21 symptom score; all six authors were from Seth GS Medical College and King Edward Memorial Hospital, Mumbai; the abstract states the sponsors had no role in the study but does not name them, so whether Natural Remedies funded it is not known, and no registry number is given in the abstract (Raj et al. 2023, Complement Ther Med)
300 participants enrolled (331 screened) with an uncomplicated upper respiratory viral infection (common cold).
On day 3, WURSS-21 scores were lower than placebo with 400 mg (mean difference -3.85, adjusted p = 0.034) and with 200 mg (mean difference -3.74, adjusted p = 0.038), and change from baseline was also better with both doses. Scores did not differ from placebo on days 5 and 7. Nasal mucus weight, tissue use and nasal IL-8 leaned toward the extract but were not significant. No participant reported adverse physical symptoms; new eosinophilia on day 3 occurred in all groups, including placebo, without a significant difference.
Open-label, single-center study without a placebo group; 100 mg capsules twice a day for 30 days; primary outcome change in natural killer cell counts; funded by Natural Remedies, and three of the eight authors were Natural Remedies employees (Rajanna et al. 2021, J Ayurveda Integr Med)
30 healthy adults with absolute lymphocyte counts of 1,000 to 4,000 cells/mm3.
Natural killer cell counts, the primary outcome, did not change significantly (day 30 p = 0.45 versus baseline). Interferon gamma and IL-4 rose and IL-2 fell by day 30 compared with baseline; total T cells and T helper cells trended upward without reaching significance in the full group, and rose significantly in a subgroup of 21. No treatment-related adverse events occurred. Without a placebo group, changes cannot be credited to the extract.
OECD-guideline acute and 90-day repeated-dose oral toxicity studies in Sprague Dawley rats at 300, 600 and 900 mg/kg a day; four of the six authors were from the Natural Remedies research center (Murugan et al. 2023, J Appl Toxicol)
Sprague Dawley rats.
No treatment-related signs of toxicity or deaths occurred after a single 5,000 mg/kg dose. Over 90 days, blood counts, blood chemistry, urine tests, organ weights and tissue examinations showed no toxicologically significant changes, and the authors set the no observed adverse effect level at 900 mg/kg a day, the highest dose tested. Animal results do not establish safety in people.