The Evidence Base

Research

Twenty-five peer-reviewed studies behind every claim we make — summarized, graded by strength, and linked to the source. Including the ones that found nothing.

How to read this page

Every study below carries a label describing what kind of evidence it is. This matters more than most wellness brands admit. A randomized controlled trial in humans and a test-tube experiment on cells are not the same thing, and we do not present them as though they were.

  • Meta-analysis — pooled results from many trials. The strongest evidence available.
  • Phase III RCT / Randomized controlled trial — humans, randomized, usually placebo-controlled.
  • Clinical trial / study — measured in humans, typically smaller or without randomization.
  • Animal model — measured in animals. Suggestive of mechanism, not proof in people.
  • In vitro — cells or enzymes in a dish. Establishes that something can happen, not that it does in you.
  • Protocol — a registered trial whose results are not yet published.

We summarize each study in our own words and link to the original. We do not reproduce publishers' abstracts. If a summary here differs from the source, the source is right — follow the DOI link and read it.

Forest Bathing & Phytoncide Exposure

9 studies

Clinical trial · 12 subjects THE CORE STUDY

Effect of phytoncide from trees on human natural killer cell function

Li Q, Kobayashi M, Wakayama Y, et al. Int J Immunopathol Pharmacol. 2009. doi:10.1177/039463200902200410

Twelve healthy men stayed three nights in an urban hotel room while hinoki cypress (Chamaecyparis obtusa) stem oil was vaporized into the room overnight. No forest was involved. Natural killer cell activity rose significantly, as did perforin, granulysin and granzyme A/B-expressing cells, while urinary adrenaline and noradrenaline fell. α-Pinene and β-pinene were confirmed present in the room air.

Why we cite it This is the closest published analogue to what a SYLVANA diffuser does: it isolates diffused tree compounds indoors as the active variable, separate from the forest, the walk, and the scenery.

Clinical trial · 12 subjects

Visiting a forest, but not a city, increases human natural killer activity and expression of anti-cancer proteins

Li Q, Morimoto K, Kobayashi M, et al. Int J Immunopathol Pharmacol. 2008. doi:10.1177/039463200802100113

Subjects took a three-day trip to forest areas and, separately, to a city, with activity levels matched between trips. The forest trip significantly raised NK activity and anti-cancer protein expression and lowered urinary adrenaline; the city trip did not. Elevated NK activity persisted more than seven days.

Why we cite it Establishes the effect is specific to the forest environment rather than to travel, rest or novelty. Phytoncides were measured in forest air and were near-absent in city air.

Meta-analysis · 732 participants, 20 trials STRONGEST EVIDENCE

Blood pressure-lowering effect of Shinrin-yoku (forest bathing): a systematic review and meta-analysis

Ideno Y, Hayashi K, Abe Y, et al. BMC Complement Altern Med. 2017. doi:10.1186/s12906-017-1912-z

Pooling 20 trials, systolic blood pressure was 3.15 mmHg lower and diastolic 1.75 mmHg lower in forest versus non-forest environments; heart and pulse rate were 3.84 bpm lower across 13 trials. Among participants with systolic pressure already at or above 130 mmHg, the reduction was 6.33 mmHg. Walking and non-walking groups showed almost identical effects (−3.48 vs −2.99 mmHg).

Why we cite it The walking-versus-sitting comparison is the key result: the authors conclude the effect is not caused by physical activity. That is what makes the benefit portable — and bottleable.

Clinical study · Nagano AKASAWA REGION

Physiological and psychological effects of forest therapy on middle-aged males with high-normal blood pressure

Ochiai H, Ikei H, Song C, et al. Int J Environ Res Public Health. 2015. doi:10.3390/ijerph120302532

Middle-aged men with high-normal blood pressure showed significantly lower systolic and diastolic pressure, urinary adrenaline and serum cortisol after forest therapy. Profile of Mood State scores for tension-anxiety, confusion and anger-hostility all fell.

Why we cite it Conducted in Agematsu, Kiso, Nagano — the Akasawa forest region that SYLVANA takes its inspiration from. Also notable for studying an at-risk group rather than healthy young volunteers.

Field experiment · 280 subjects

The physiological effects of Shinrin-yoku: evidence from field experiments in 24 forests across Japan

Park BJ, Tsunetsugu Y, Kasetani T, Kagawa T, Miyazaki Y Environ Health Prev Med. 2010. doi:10.1007/s12199-009-0086-9

Across 24 forests, 280 subjects walked in and viewed forest and city areas in a cross-over design. Forest environments produced lower salivary cortisol, lower pulse rate, lower blood pressure, greater parasympathetic activity and lower sympathetic activity.

Why we cite it One of the largest field datasets in the literature, and the origin of much of the pooled physiological data quoted elsewhere.

Randomized controlled trial

Physiological effects of Shinrin-yoku in an old-growth broadleaf forest in Yamagata Prefecture, Japan

Tsunetsugu Y, Park BJ, Ishii H, Hirano H, Kagawa T, Miyazaki Y J Physiol Anthropol. 2007. doi:10.2114/jpa2.26.135

Blood pressure and pulse rate were significantly lower in the forest area than the city area, salivary cortisol was significantly lower, and heart rate variability shifted toward parasympathetic dominance. Subjective ratings of comfort, calm and refreshment were significantly higher.

Why we cite it An early controlled demonstration pairing physiological measures with subjective report, in an old-growth forest setting.

Review · 420 subjects, 35 forests

Forest medicine research in Japan

Miyazaki Y, Ikei H, Song C Nihon Eiseigaku Zasshi. 2014. doi:10.1265/jjh.69.122

Reviewing field experiments involving 420 subjects across 35 forests, subjects sitting in natural surroundings showed a 12.4% decrease in cortisol, 7.0% decrease in sympathetic activity, 1.4% decrease in systolic blood pressure and 5.8% decrease in heart rate, alongside a 55.0% increase in parasympathetic activity. NK activity rose 56% and remained 23% elevated at one month.

Why we cite it The source of the pooled percentage figures quoted on our homepage.

Randomized controlled trial · 48 adults

Physiological benefits of forest environment: based on field research at 4 sites

Lee J, Park BJ, Tsunetsugu Y, Kagawa T, Miyazaki Y Nihon Eiseigaku Zasshi. 2011. doi:10.1265/jjh.66.663

Across four sites, 48 young male adults showed significantly higher parasympathetic and lower sympathetic indices, plus lower systolic and diastolic blood pressure, pulse rate and salivary cortisol, in forest versus urban environments.

Why we cite it A tightly controlled replication across multiple independent sites.

Review

Effects of forest environment (Shinrin-yoku/forest bathing) on health promotion and disease prevention — the establishment of Forest Medicine

Li Q Environ Health Prev Med. 2022. doi:10.1265/ehpm.22-00160

A summary of two decades of forest medicine research: increased NK activity and anti-cancer proteins, reduced blood pressure and heart rate, reduced urinary adrenaline/noradrenaline and salivary cortisol, stabilised autonomic balance, improved sleep, and improved Profile of Mood State scores.

Why we cite it The field's most recent overview, written by the researcher who founded it.

Terpene Pharmacology

9 studies

Receptor pharmacology LANDMARK PAPER

Beta-caryophyllene is a dietary cannabinoid

Gertsch J, Leonti M, Raduner S, et al. Proc Natl Acad Sci USA. 2008. doi:10.1073/pnas.0803601105

(E)-β-caryophyllene binds selectively to the CB2 cannabinoid receptor with a Ki of 155 nM and functions as a full CB2 agonist, inhibiting adenylate cyclase and reducing LPS-induced pro-inflammatory cytokine expression in human monocytes. Oral administration reduced inflammatory response in wild-type mice but not in CB2-knockout mice.

Why we cite it The definitive identification of a common plant volatile as a selective cannabinoid receptor agonist — with no psychoactivity. The CB2-knockout comparison is what makes the mechanism airtight.

Animal model

The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects

Klauke A-L, Racz I, Pradier B, et al. Eur Neuropsychopharmacol. 2014. doi:10.1016/j.euroneuro.2013.10.008

Orally administered β-caryophyllene reduced inflammatory pain responses in a CB2-receptor-dependent manner and attenuated thermal hyperalgesia, mechanical allodynia and spinal neuroinflammation in a neuropathic pain model, with no tolerance developing over prolonged treatment.

Why we cite it Confirms that CB2 engagement by β-caryophyllene produces measurable downstream effects in a living animal, not only in receptor assays.

Randomized controlled trial · 24 humans HUMAN TRIAL

Chirality influences the effects of linalool on physiological parameters of stress

Höferl M, Krist S, Buchbauer G Planta Med. 2006. doi:10.1055/s-2006-947202

Twenty-four human subjects under experimental stress inhaled R-(−)- and S-(+)-linalool while heart rate, blood pressure, electrodermal activity and salivary cortisol were monitored. Both enantiomers modulated salivary cortisol and exerted relaxing effects, with the two forms differing in their effects on other parameters.

Why we cite it Direct human evidence that an inhaled terpene measurably changes a stress hormone. The chirality finding also underlines why the specific form of a compound matters in formulation.

Animal model

Inhalation of (R,S)-linalool by rats experiencing restraint stress alters neuropeptide and MHC class I gene expression in the hypothalamus

Yoshida K, Yamamoto N, Fujiwara S, Kamei A, Abe K, Nakamura A Neurosci Lett. 2017. doi:10.1016/j.neulet.2017.05.046

Microarray analysis of the hypothalamus in restraint-stressed rats found that inhaled linalool restored expression of 560 stress-induced gene probes toward normal, including genes for the anxiolytic neuropeptides oxytocin and neuropeptide Y.

Why we cite it Offers a molecular mechanism for the calming effect observed behaviorally and in human cortisol measurements.

Pilot study · 70 residents

The effect of eucalyptol on nursing home residents

Goto S, Suzuki H, Nakagawa T, Shimizu K Scientific Reports. 2020. doi:10.1038/s41598-020-61045-8

Eucalyptol was diffused into the bedrooms of 70 nursing-home residents with cognitive impairment. Dementia Behavior Disturbance scale scores improved significantly — including among residents exposed only to unperceivable levels drifting in from a communal room. Mini Mental State Examination and agitation inventory scores did not change.

Why we cite it We cite the MMSE null result alongside the positive finding. The behavioral improvement is real; a claim of general cognitive enhancement would not be supported by this study.

Clinical study · 26 humans

Autonomic responses during inhalation of natural fragrance of Cedrol in humans

Dayawansa S, Umeno K, Takakura H, et al. Auton Neurosci. 2003. doi:10.1016/j.autneu.2003.08.002

Twenty-six subjects inhaled vaporized cedrol via face mask. Heart rate, systolic and diastolic blood pressure and respiratory rate all fell significantly versus blank air, baroreceptor sensitivity increased, and heart rate variability shifted toward parasympathetic dominance.

Why we cite it A clean, controlled demonstration of a single isolated terpene producing cardiovascular change in humans.

Clinical study MECHANISM

Effects of direct cedrol inhalation into the lower airway on autonomic nervous activity in totally laryngectomised subjects

Umeno K, Hori E, Tsubota M, et al. Br J Clin Pharmacol. 2008. doi:10.1111/j.1365-2125.2007.02992.x

Cedrol was delivered directly into the trachea of totally laryngectomised subjects, bypassing the nose and the sense of smell entirely. Systolic and diastolic blood pressure still fell significantly, baroreceptor sensitivity increased, and sympathetic indices decreased.

Why we cite it Critical for understanding how these compounds work: the effect persisted in people who could not smell the compound. This is pharmacology via the airway, not a psychological response to a pleasant scent.

In vitro IN VITRO ONLY

In-vitro inhibition of human erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes

Perry NS, Houghton PJ, Theobald A, Jenner P, Perry EK J Pharm Pharmacol. 2000. doi:10.1211/0022357001774598

α-Pinene and 1,8-cineole inhibited human erythrocyte acetylcholinesterase, the enzyme that degrades the memory-associated neurotransmitter acetylcholine, with IC50 values of 0.63 mM and 0.67 mM respectively. The essential oil as a whole was more potent than any single constituent, suggesting synergy.

Why we cite it We flag this one carefully. The authors state explicitly that whether these in-vitro results translate to effects on brain acetylcholinesterase in a living person remains to be determined.

Protocol RESULTS PENDING

Evaluating the relaxation effects of Shikuwasa (Citrus depressa) essential oil inhalation in young female adults: study protocol for a randomised controlled trial

Yamaguchi F, Yoshinaga N, Kuroki M, et al. Contemp Clin Trials Commun. 2024. doi:10.1016/j.conctc.2024.101342

A registered two-arm randomized controlled trial protocol testing inhalation of a limonene-dominant citrus essential oil against odour-free air, measuring subjective tense arousal, miosis rate, peripheral skin temperature and cerebral blood flow.

Why we cite it Listed because we cite limonene in two formulations and want to be transparent that the strongest human evidence for it is a trial still in progress, not a completed result.

Dragon's Blood — Croton lechleri

7 studies

Regulatory review FDA-APPROVED DRUG

Crofelemer: a review of its use in the management of non-infectious diarrhoea in adult patients with HIV/AIDS

Frampton JE Drugs. 2013. doi:10.1007/s40265-013-0083-6

Crofelemer is a botanical drug substance — an oligomeric proanthocyanidin — extracted from the stem bark latex of the Croton lechleri tree. It acts locally in the gastrointestinal tract by inhibiting two chloride ion channels, with minimal systemic absorption. It is the first and so far only agent approved by the US FDA for symptomatic relief of non-infectious diarrhoea in adults with HIV/AIDS on antiretroviral therapy.

Why we cite it This is the single most important fact about dragon's blood, and it has nothing to do with antioxidant scores: the proanthocyanidins in this tree were rigorous enough to become an approved prescription medicine.

Phase III RCT · 376 patients PHASE III

Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT trial)

Macarthur RD, Hawkins TN, Brown SJ, et al. HIV Clin Trials. 2013. doi:10.1310/hct1406-261

A randomized, double-blind, placebo-controlled, two-stage phase III trial in 376 patients. Significantly more patients receiving crofelemer 125 mg twice daily achieved clinical response versus placebo (17.6% vs 8.0%), with greater improvement in daily watery bowel movements and stool consistency. The drug was minimally absorbed and its safety profile was comparable to placebo.

Why we cite it The registration trial behind the FDA approval — the level of evidence almost no botanical ingredient ever reaches.

Phase II RCT · 51 patients

A double blind, randomized, placebo-controlled phase II study of orally administered SP-303 for diarrhea in patients with AIDS

Holodniy M, Koch J, Mistal M, et al. Am J Gastroenterol. 1999. doi:10.1111/j.1572-0241.1999.01535.x

Fifty-one patients received SP-303 (the proanthocyanidin extract later developed into crofelemer) or placebo. Over four days of treatment, the SP-303 group showed significant reductions in stool weight and abnormal stool frequency versus placebo, with no serious adverse events.

Why we cite it The earlier trial that established safety and initial efficacy for the extract, two decades before approval.

RCT · 242 patients NEGATIVE RESULT

Evaluation of crofelemer in the treatment of diarrhea-predominant irritable bowel syndrome patients

Mangel AW, Chaturvedi P Digestion. 2008. doi:10.1159/000185719

In 242 patients with diarrhoea-predominant IBS, crofelemer did not produce significant improvement in stool consistency, the primary endpoint. A secondary finding of increased pain- and discomfort-free days was seen in female patients only.

Why we cite it We include this deliberately. The compound failed its primary endpoint in this indication. A reference list that contains only supportive findings is a marketing document, not an evidence base.

Systematic review

Review of sangre de drago (Croton lechleri) — a South American tree sap in the treatment of diarrhea, inflammation, insect bites, viral infections, and wounds

Jones K J Altern Complement Med. 2003. doi:10.1089/107555303771952235

A review of in-vitro, in-vivo and clinical evidence for the traditional uses of Croton lechleri sap. Results largely support use for wound healing, inflammation, insect-bite symptoms and diarrhoea. The author notes the sap showed low toxicity and was well tolerated in clinical studies, and stresses that chemical composition varies by geographic origin.

Why we cite it The broadest overview of the ingredient's documented activity, and the source of our position that material must be standardized.

In vitro IN VITRO ONLY

Croton lechleri sap and isolated alkaloid taspine exhibit inhibition against human melanoma SK23 and colon cancer HT29 cell lines

Montopoli M, Bertin R, Chen Z, Bolcato J, Caparrotta L, Froldi G J Ethnopharmacol. 2012. doi:10.1016/j.jep.2012.10.032

Croton lechleri sap inhibited proliferation of human melanoma cells from concentrations as low as 1 µg/mL, with higher concentrations required for colorectal lines. The isolated alkaloid taspine showed activity at 0.1 µg/mL and caused changes to microtubule structure and cell morphology.

Why we cite it Cell-culture work only. It tells us the sap is biologically active; it says nothing about effects in a human being, and we make no such claim.

Phytochemical analysis · 22 sites SOURCING

Geographic distribution of three alkaloid chemotypes of Croton lechleri

Milanowski DJ, Winter REK, Elvin-Lewis MPF, Lewis WH J Nat Prod. 2002. doi:10.1021/np000270v

Latex and leaf samples from 22 sites across northern Peru and Ecuador were analyzed by HPLC. Taspine averaged around 9% of the latex by dry weight, but three distinct alkaloid chemotypes were identified with different geographic distributions.

Why we cite it The reason sourcing and batch testing matter for this ingredient: two samples of dragon's blood from different regions are not chemically identical.

Limits

What this evidence does not show

An honest evidence base has to include its own boundaries. Here are ours.

  • No trials have been run on SYLVANA products. Every study here examines forest environments, diffused tree oils, or isolated compounds. None of them tested our formulations. When we say "documented," we mean documented for the compound — not for our bottle.
  • Four compounds have thin human evidence. Terpinolene, valencene, myrcene and nerolidol appear in our formulations for aromatic and traditional reasons. The published human data on them is limited, and we label them that way rather than inventing effects.
  • Limonene's mood mechanism is not established in humans. It is widely described as affecting dopamine and serotonin. The strongest human trial we could find is a protocol whose results are not yet published.
  • ORAC is a laboratory assay, not a health outcome. The USDA withdrew its ORAC database in 2012 because in-vitro antioxidant values have not been shown to predict effects in the body. We publish dragon's blood ORAC figures as laboratory measurements only.
  • Most forest studies measure immediate effects. Only two of the twenty trials in the Ideno meta-analysis ran longer than a day, and one found the benefit had faded eight weeks after a three-day programme. Repeated exposure appears to be necessary — which is the argument for daily use, not a claim of permanent change.