Benefits
Skin health in infants from allergy-prone families
In a New Zealand trial of 474 infants at high allergy risk, HN001 at 6 billion CFU a day (mothers from 35 weeks of pregnancy, infants from birth to age 2) roughly halved cumulative eczema by age 2 versus placebo (hazard ratio 0.51). The gap held to ages 4, 6 and 11. HN019 had no effect in the same trial.
Infant skin when only the mother takes the probiotic
A second trial gave HN001 at 6 billion CFU a day to 423 pregnant women from mid-pregnancy to 6 months after birth, without dosing the infant. Infant eczema, wheeze and sensitization at 12 months did not differ from placebo, and HN001 was not found in breast milk. The gap versus the mother-and-infant trial was not statistically significant.
Postpartum mood and anxiety scores
In the same pregnancy trial, mothers on HN001 reported lower depression scores (7.7 versus 9.0) and anxiety scores (12.0 versus 13.0) after birth than mothers on placebo, and fewer screened positive for clinically relevant anxiety. Mood was a secondary outcome; the trial's primary outcome, infant eczema at 12 months, did not differ.
Perceived stress and happiness in adults
Three later HN001 trials at 6 billion CFU a day found no significant difference from placebo on their primary outcomes: perceived stress in 483 students before exams, perceived stress in 600 nurses over 12 weeks, and happiness scores in 120 stressed adults over 28 days, where only post-hoc time trends favored HN001.
Blood sugar tests during pregnancy
In the pregnancy trial, gestational diabetes by the international definition was lower on HN001 but not significantly (relative risk 0.59, P=0.08); by the stricter New Zealand definition it was 2.1% versus 6.5% (P=0.03). A 6-month trial in 153 adults with raised blood sugar found no change in HbA1c or other metabolic outcomes.
Natural killer cell activity in older adults
In a small pre-post study without a placebo group, 27 healthy older adults drank milk with HN001 or B. lactis HN019 for 3 weeks. Blood natural killer cell tumor-killing activity rose by an average of 101% on HN001. These are laboratory immune markers, not measured changes in infections.
Stool consistency with a two-strain HN019 and HN001 blend
In a 4-week trial in 250 adults with constipation, a blend led by B. lactis HN019 (15.4 billion CFU a day) with a smaller HN001 dose (3.8 billion CFU a day) and oligosaccharides showed no time-by-group effect on stool form, bowel movement frequency or straining, though stool form improved within the group and its 4-week change favored the blend over placebo. HN001 was not tested alone.
Mechanism of action
Passage through the gut and early colonization
In the infant trial, HN001 was detected in the stool of 71.5% of infants at 3 months, compared with 22.6% for HN019, showing that the strain survives passage through the gut. Detection rates of the two strains were similar by 24 months.
Strain-specific effects
In the same trial, the infant skin effect was seen with HN001 but not with B. lactis HN019 given the same way, and the investigators concluded that benefits may be species specific. Results for HN001 should not be assumed for other L. rhamnosus strains such as GG, or the reverse.
Direct infant exposure rather than breast milk transfer
When only mothers took HN001, the strain could not be detected in their breast milk and breast milk TGF-beta and IgA profiles were unchanged. This fits the finding that only the trial that also dosed infants saw a skin result, although the difference between the two trials was not statistically significant.
Clinical trials
Two-center, double-blind, randomized, placebo-controlled trial (ACTRN12607000518460); HN001 6 billion CFU/day or B. lactis HN019 9 billion CFU/day, taken by mothers from 35 weeks of pregnancy to 6 months postpartum if breastfeeding and by infants from birth to age 2; follow-ups at 4, 6 and 11 years. Funders listed for the 11-year report include Fonterra, the Health Research Council of New Zealand and Cure Kids (Wickens et al. 2008, J Allergy Clin Immunol)
474 infants at high risk of allergic disease; 425 seen at age 4.
HN001 lowered cumulative eczema by age 2 (hazard ratio 0.51, P=0.01); HN019 did not (0.90). Skin-prick sensitization at age 2 did not differ. The HN001 effect on eczema held at age 4 (0.57), 6 (0.56) and 11 (0.58), with lower sensitization at 6 and 11 years. HN019 had no significant effect on any outcome.
Two-center, double-blind, randomized, placebo-controlled trial (ACTRN12612000196842); HN001 6 billion CFU/day or maltodextrin placebo from 14 to 16 weeks of pregnancy to 6 months postpartum if breastfeeding; infants not dosed. Funded by the Health Research Council of New Zealand (11/318) and Fonterra, which also ran randomization (Slykerman et al. 2017, EBioMedicine)
423 pregnant women with a personal or partner history of allergy; 380 completed the mood questionnaires.
Secondary outcome: postpartum depression scores (7.7 versus 9.0) and anxiety scores (12.0 versus 13.0) were lower on HN001, and screen-positive anxiety was less common (OR 0.44). In the same trial, infant eczema at 12 months, the primary outcome, did not differ, and gestational diabetes was not significantly lower by the main definition (RR 0.59, P=0.08).
Randomized, double-blind, placebo-controlled trial; HN001 6 billion CFU/day for one semester (8 to 13 weeks); funded by Fonterra (Slykerman et al. 2022, PLoS One)
483 undergraduate students in Auckland; 391 completed the post-intervention questionnaires.
Null result: stress, anxiety and psychological well-being did not differ between HN001 and placebo. COVID-19 restrictions moved teaching and exams online during the trial, which the authors said may have changed the usual stress pattern. No adverse events were reported.
Randomized, double-blind, placebo-controlled trial; HN001 6 billion CFU/day for 12 weeks during 2020; Fonterra provided funding and capsules and managed randomization (Slykerman et al. 2022, Sci Rep)
600 nurses in New Zealand enrolled; 484 completed.
Null result: perceived stress, the primary outcome, and the average number of days with viral illness symptoms did not differ between HN001 and placebo. Stress and illness fell in both groups during a year when COVID-19 was eliminated from the community.
Randomized, double-blind, placebo-controlled trial; Nutiani HN001 capsules providing 6 billion CFU/day for 28 days; funded by Fonterra, which employed both authors (Al Kassaa et al. 2024, Nutrients)
120 adults aged 18 and over with mild to high perceived stress.
Primary outcome not significant: happiness scores rose 13.3 points on HN001 and 10.2 on placebo, and perceived stress fell 8.1 versus 6.6. Post-hoc analyses found significant time-by-group interactions (P=0.014 and 0.043). Adverse events were reported by 3 people on HN001 and 6 on placebo.
2x2 factorial randomized, placebo-controlled trial (ACTRN12617000990325); HN001 6 billion CFU/day capsules and/or cereal with 4 g/day oat beta-glucan for 6 months; funded by the Health Research Council of New Zealand, the New Zealand Ministry of Health and the Healthier Lives National Science Challenge, with capsules supplied by Fonterra (Barthow et al. 2022, BMJ Open)
153 community adults aged 18 to 80 with HbA1c 41 to 49 mmol/mol; 129 with complete HbA1c data.
Null result: HbA1c at 6 months did not differ between HN001 and placebo capsules (difference -0.83 mmol/mol, p=0.63), and no secondary outcome differed, including blood glucose, insulin, lipids, blood pressure, body weight and mental well-being.
Pre-post intervention study without a placebo group; a run-in on milk alone, then low-fat, low-lactose milk with HN001 or B. lactis HN019 for 3 weeks (Gill et al. 2001, J Clin Immunol)
27 healthy older volunteers.
The share of CD56-positive lymphocytes and the tumor-killing activity of blood immune cells in the lab rose after either strain, by an average of 101% on HN001 and 62% on HN019, with larger rises in people over 70. These are laboratory markers; infections were not measured.
4-week double-blind, randomized, placebo-controlled trial (NCT04667884) of three fiber formulas and one probiotic blend: B. lactis HN019 15.4 billion CFU/day plus HN001 3.8 billion CFU/day with oligosaccharides; supplements provided by BYHEALTH (Lai et al. 2023, Gut Microbes)
250 adults with functional constipation; 242 completed.
No time-by-group effect on bowel movement frequency, stool form score or straining. Stool form improved within each active group but not on placebo, and the 4-week change favored the active groups. HN019 was the lead strain and HN001 was not tested alone.