Eleutherococcus senticosus (synonymous with Acanthopanax senticosus and sometimes referred to as Siberian ginseng or Ciwujia) is an Adaptogenthat has traditional usage in asian countries (China, Japan, Korea, and eastern Russia) although its popularity is lesser than that of asian ginseng (Panax ginseng). It's properties according to Traditional Chinese Medicine are "invigorating qi and strengthening the spleen, tonifying kidney to relieve mental strain" whereas usage in Siberia (from where the plant appears to originate) and Russia tends to be associated with promoting physical endurance, non-specific immunity, and longevity.
Traditional usage of eleuthero involves eating the root or its extracts in the dosage range of 9-27g a day (chinese medicine) or 6-12g a day (American sources, more modern); these are both higher than a more commonly recommended 2-4 grams of eleuthero root. The root itself is a light brown, free-flowing powder that has a somewhat sweet flavour with bitter undertones.
Eleuthero is a root that has been used in Traditional Chinese Medicine mostly for its anti-fatigue purposes and some pro-vitality and longevity purposes in older individuals as well
The roots and/or leaves of eleuthero, the main component used, tend to contain:
Eleutheroside B, E, E1, and E2 (lignans) which are structurally based off of episyringaresinol. Syringoresinol is also present, and Eleutheroside B is merely syringin and appears to be the main bioactive lignan. Total eleutherosides appear to range from 0.6-0.9% of the dry weight of the root and usually 0.31% and 0.51% are reference levels for eleutheroside B and E, respectively
Ciwujianosides (A1, A2, A3, A4, B, C1, C2, C3, C4, D1, D2 D3, E)
Acanthopanaxosides A-C (triterpene saponins) and E
Eleutherazine A and B (Aerial parts)
Oplopanone B (Aerial parts)
Mesembryanthemoidigenic acid (as 3-O-alpha-rhamnopyranosyl-
Hederasaponin B and its glycoside, 3-O-beta-D-glucuronopyranoside 6'-O-methyl ester
Gypsogenin (as 3-O-beta-D-glucuronopyranoside)
(+)-pinoresinol-di-O-β-d-glucoside and (+)-pinoresinol-O-β-d-glucoside
Isofraxidin (as 7-O-β-D-glucoside), structurally related to scopoletin
Quercetin, quercitrin, and rutin
Chlorogenic Acid and caffeic acid derivatives
Eleuthero contains both saponins and lignans, with a large amount (over 200) different molecules being detected as either aglycones or glycosides. The main bioactive appears to be Eleutheroside B (Syringin) and Eleuetheroside E (a syringaresinol diglucoside) and these are not structurally related to Panax ginseng bioactives
The essential oil of eleuthero (0.05% of the root) contains:
Possesses an aromatic component, but there is no literature currently assessing the possible usage of eleuthero in Aromatherapy
The polysaccharides of eleuthero root include:
The root contains polysaccharides that appear immunostimulatory in nature, although this may not apply to encapsulated eleuthero supplements (polysaccharides are carbohydrates, and they tend to be extracted out of the product in favor of the lignans and triterpenoids)
The bioavailability of eleutheroside B and E has been determined to be 3.30+/-0.63% and 3.82+/-0.86% in rats, respectively.
Mechanisms of absorption not well studied at this moment in time, but absorption appears to be fairly poor
Oral ingestion of eleutheroside B has found a Tmax of 0.45+/-0.112 hours (isolated molecule) or 0.583+/-0.144 hours (water extract of eleuthero) with a Cmax of 78.25+/-15.80μg/L and 97.75+/-12.64μg/L (isolated molecule and water extract) with a half life of 1.47-2.03 hours and an AUC0−∞ 130.19+/-34.54μg/h/L (isolated) or 193.89+/-55.46μg/h/L (water extract).
Eleutheroside E has been noted to have a Tmax of 0.42+/-0.14 or 2.75+/-2.17 hours (isolated and water extract) reaching Cmax values of 91.33+/-12.53μg/L and 75.50+/-26.62μg/L with half-lives of 1.13+/-0.43 and 1.49+/-0.18 hours and an AUC0−∞ of 135.19±32.27μg/h/L in isolation and 375.14±87.90μg/h/L in aqueous solution.
Isofraxidin (isolated isofraxidin) noted that the oral doses of 7.5mg/kg and 15mg/kg isofraxidin reached Cmax values of 6.56+/-0.10µg/mL and 13.80+/-2.19µg/mL at Tmax values of 0.19+/-0.03 and 0.23+/-0.03 hours with half-lives of 0.51-0.57 hours and AUC0−∞ values of 22.85+/-4.26µg/h/mL and 45.14+/-7.33µg/h/mL. These numbers were slightly higher with the same dose of isofraxidin via eleuthero root, reaching an AUC of 124.98µg/h/mL at the higher dose after 24 hours.
The three main agents of eleuthero have been detected in serum following oral ingestion, and appear to be better absorbed when consumed via the whole root extract relative to being consumed as an isolated molecule
When eleutheroside B and E are injected into rats they can be detected in the liver, kidney, spleen, and heart (descending order of concentration of eleutheroside E, eleutheroside B detected in kidney, liver, and heart).
Eleutherosides have been detected in organs following oral ingestion, but the degree of evidence assessing this is not substantial
2.4. Enzymatic Interactions
485mg of eleuthero root has failed to significantly influence CYP2D6 or CYP3A4 activity which replicates previous in vitro data showing no effect of eleuthero component on CYP3A4 activity in human liver microsomes.
Currently no known enzyme interactions that would interfere with pharmaceuticals
Ingestion of 2000mg/kg eleuthero to mice for a week appears to exert anti-depressive effects and associated with whole-brain upregulation of cAMP response element-binding and monoamines (serotonin, noradrenaline, and dopamine). This increase in catecholamines has been noted elsewhere (measured in the hypothalamus) at 100-250mg/kg intake in rats and an increase in noradrenaline turnover has been noted in the hypothalamus as well. The mechanisms underlying the increase in catecholamines are not yet known, but may be related to modulation of catechol-o-methyltransferase (one of the target enzymes from Green Tea Catechins).
When looking at c-Fos immunoreactivity, there appears to be a larger induction of imunoreactivity following oral ingestion of 100mg/kg eleuthero in the paraventricular nuclei and the caudal portion of the supraoptic nuceli; two regions involed in chronic stress.
Eleuthero appears to be catecholaminergic in nature (similar to the Adaptogen Muira puama) and able to increase neurotransmitters. The dosage this occurs at may be practically relevant to supplemental doses (100-250mg/kg of the root extract to a rat is 16-40mg/kg for a human, and a 150lb human would need 1.1-2.7g of the dry root)
Syringin has been implicated in promoting neurite outgrowth in PC12 cells, although to a lesser degree relative to (+)-syringaresinol diglucoside and aucubin (from Aucuba japonica).
Possible positive growth on neurites, but not well studied or replicated. Some literature behind a russian paywall suggesting an increase in cognition that cannot be assessed|published=2003 Sep-Oct|authors=Arushanian EB, Baĭda OA, Mastiagin SS, Popova AP, Shikina IB|journal=Eksp Klin Farmakol]
It is thought that the release of Neuropeptide Y seen with adaptogens can be used as a biomarker of stress reduction from adaptogens, this was subsequently tested with Adapt232 (Schisandra chinensis, Rhodiola Rosea, and eleuthero) in military personnel (prone to cardiovascular stress responses due to chronic stress to a higher level than seen in the average population which is correlated with trauma) noted reductions in blood pressure (systolic and diastolic) and heart rate with treatment which was said to be due to neuropeptide Y regulation (it is not clear if this study measured NPY).
This adaptogen complex (ADAPT232) also appears to induce HSP72 induction from neuroglia which has been detected in the serum of rats given the combination therapy prior to a swimming stress test.
Neuropeptide Y appears to be related to chronic stress, and it is thought that this is a molecular target of adaptogenic compounds. Studies assessing this tend to use ADAPT232 (Eleuthero with Rhodiola and Schisandra chinensis) and there is insufficient evidence to evaluate eleuthero in isolation on this parameter
One study assessing isolated eleutheroside E at 10 or 50mg/kg (injections) is able to normalize a fair bit of the alterations observed during sleep deprivation in mice and a normalization of the changes in erythropoeisis induced by sleep deprivation (suppression, normally) were noted to occur with adaptogens including eleuthero supplementation in mice thought to be secondary to modulating neuroamines.
May aid function in sleep deprivation, although there are no studies assessing the potency of eleuthero relative to other agents for reference
Eleuthero (fruit extract at 1-40µg/mL) has been noted to induce the enzyme known as heme oxygenase 1 (HO-1) secondary to p38-CREB induced translocation of Nrf2 (p38 MAPK also phosphorylated). HO-1 is a rate-limiting enzyme of antiinflammation in many cells including microglia which reduced the expression of proinflammatory mediators like iNOS and COX-2. The induction of HO-1 from eleuthero is concentration-dependent and up to 5-7 fold control cells at 40µg/mL (HT22 and BV2 cells, respectively).
Eleuthero fruit extracts have also been noted to reduce glutamate-induced oxidation in microglia and preserve cell viability in the presence of excitotoxicity in a concentration dependent manner (40µg/mL preserving approximately 80% of viability).
In rat corticol neurons damaged by amyloid β(25-35), both main eleuterosides (B and E) and isofraxidin showed protective effects in the concentration range of 1-10μM and both the butanolic (100μg/mL) and water (1-100μg/mL) extracts of the roots in general was able to normalize damage (similar to the active control of 100ng/mL NGF). This has been noted elsewhere where eleutheroside B was again the most protective agent.
In vitro, there appear to be neuroprotective effects of eleuthero root extracts related to antioxidant enzyme induction. These might be occurring at feasible concentrations (no brain pharmacokinetic data, however)
Oral ingestion of 30, 100, and 300mg/kg eleuthero (stem bark with 0.486+/-0.046% eleutheroside E) was able to preserve 3.5%, 25.9% and 53.1% of hippocampal cell viability when rats were subject to ischemia/reperfusion and then give the oral dose of eleuthero immediately after and 90 minutes after surgery. This study also noted that with the preservation of hippocampal cells came preservation of spatial memory in a Y-Maze test, with the highest dose inhibiting 81.9% of the losses in spatial memory.
The injury induced increase in inflammatory parameters (COX2 induction and activated microglia) has also been noted to be markedly attenuated 7 days after the injury as assessed by histological examination, and these protective effects have been replicated elsewhere but with 100mg/kg injections of eleutherococcus.
Has demonstrated rehabilitative effects on one animal model of cognitive damage, with the higher tested dose (300mg/kg in rats, human estimated dose of 48mg/kg) being quite profoundly protective via mixed antiinflammatory and antioxidative
3.6. Bipolar Disorder
In a trial on adolescents already using lithium for bipolar disorder and then given either eleuthero root (750mg thrice a day for 2250mg total) or fluoxetine (20mg) for 6 weeks, there were no apparent differences in remission (51.4% vs 48.7%) or response rates (67.6% vs 71.8%) between groups although there appeared to be less side-effects assocaited with eleuthero (4) in comparison to fluoxetine (12).
A lone trial suggesting that adding high dose eleuthero to lithium was as effective as adding fluoxetine to lithium for the treatment of bipolar disorder
One study conducted in postmenopausal women given eleuthero (500mg thrice daily for a total dose of 1500mg) noted that despite insignificant changes in lipid peroxidation and antioxidant potential of the blood that a significant reduction in protein carbonyl content of immune cells (33% reduction from 0.18+/-0.10 to 0.12+/-0.05nmol/mg) and less DNA damage as assessed by comet assay (12%, 14.7%, and 7.4% in percent of tail DNA, moment, and length respectively). Protein carbonylation is thought the be somewhat of an indicator of longevity in various species.
In nematodes (C. Elegans), both eleutherococcus senticosus and Rhodiola Rosea appear to have life extension properties in the range of 10-20% while both are characterized by a shortening of life when overdosed to 10-fold the effective dose. It is thought that these act via hormetic mechanisms.
Theoretically possible that eleuthero (as well as other adaptogens) can act on a mechanism to promote longevity, although there is insufficient evidence to currently claim that eleuthero can promote longevity
One study conducted in older persons assessing quality of life after being given 300mg eleuthero root daily for 8 weeks noted to increase social functionining and some aspects of mental cognition in these elderly persons.
Eleuthero has once been noted to improve social functioning and some markers of cognitive decline in elderly persons
Although a few molecules found in eleuthero have been found to inhibit the pancreatic lipase enzyme, other have noted stimulatory properties.
Unclear influences on lipid absorption, no studies conducting a fecal analysis
One study which found benefit with both Rhodiola Rosea and Aralia mandshurica (16mg/kg for 5 days) in reducing arrythmia during ischemia/reperfusion failed to find such a protective effect associated with eleuthero. Chronic ingestion of eleuthero, similar to the two aforementioned adaptogens, elevated the ventricular fibrillation threshold in rats with postinfarction cardiosclerosis.
Ingestion of 1500mg eleuthero extract daily for 6 months is associated with a reduction of LDL-C (13.5%) relative to placebo in postmenopausal women without significantly affecting HDL-C, total cholesterol, or triglycerides.
6Interactions with Glucose Metabolism
Isolated eleutheroside B (syringin) appears to be able to acutely reduce blood glucose levels in diabetic rats and has been noted to do so in normal mice additionally which appears to be secondary to stimulating beta-endorphin release from the adrenal medulla; bilateral adrenalectomy and the presence of opioid receptor antagonists abolished this effect. Blocking the M3 muscarinic acetylcholine receptor has additionally blocked this effect (no effect of nicotinic acetylcholine blockade), and acetylcholinesterase inhibitors can increase the glucose lowering efects of syringin; alpha2-adrenergic blockade is ineffective in modifying the release of insulin, and decreased sympathetic tone increases the actions of syringin on insulin release.
Eleuthero may stimulate insulin release from the pancreas secondary to acetylcholine stimulation, which would then reduce blood glucose. No studies currently conducted in humans
7.1. Weight Gain
One study in rats using 500mg/kg eleuthero for 12 weeks noted that weight gain over the trial was reduced in both diabetic (13.4%) and normal (25.3%) rats relative to their own controls independent of changes in food intake (and thought to be related to a higher food efficiency ratio).
8Skeletal Muscle and Physical Performance
170mg/kg of a 70% methanolic extract has shown anti-oxidative effects in the skeletal muscle of mice during exercise.
8.2. Fatigue and Performance
When rats were subject to prolonged swimming, a water extract of the stem (500mg/kg for 25 days) appears to have anti-fatigue effects which was thought to be due to the (+)-syringaresinol-di-O-beta-D-glucoside component (similarly effective at 50mg/kg). This has been noted elsewhere, where five different extracts of eleuthero were tested with the one lowest in eleutherosides B and E failing to have any effect and the one with the highest Eleutheroside E content (3.32% of the 1g/kg dose) outperfoming red Panax ginseng; a time-dependent effect was noted, with days 5 and 7 outperforming day 1 and elsewhere in mice swimming performance has been enhanced with extracts containing high levels of Eleutheroside E and E2 but to a slightly lesser potency than red ginseng.
Anti-fatigue effects seem to be related to Eleutheroside E and (+)-syringaresinol-di-O-beta-D-glucoside components. When comparing eleuthero to panax ginseng they seem somewhat comparable in efficacy
When tested in humans (n=9) subject to a 75% VO2 max cycle to exhaustion, 800mg of eleuthero root (0.11% eleutheroside B and 0.12% eleutheroside E) in two divided doses with meals for 8 weeks was associated with improvements in time to exhaustion (placebo improved 6%, eleuthero improved 25.5%) paired with an increase in VO2, heart rate (4.3%), free fatty acids (19.5%) and respiratory exchange ratio (2.7%) with a decrease in glucose during exercise (6.7%) with no influence on the rate of perceived exertion. This increase in lipid oxidation has been noted elsewhere with the herb, although with a reduced heart rate.
Performance enhancement has been noted elsewhere with a 35% ethanolic extract of eleuthero in liquid form (Taiga Wurzel at 25 drops daily) for 30 days prior to a VO2 max test where max VO2 in relation to body weight increased by 8.6% (without comparison to body weight, the benefit was not statistically significant) and max VE increased by 7.4%; this study failed to note changes in the respiratory quotient or heart rate, and eleuthero outperformed Echinacea (purpurea) and elsewhere a VO2 max test on a weighted cycle ergometer noted a 23.3% increase in workload (cycle time and resistance worked against) relative to control, which outperformed the 7.3% increase in placebo (relative to control) after 8 days of ingesting 4mL of eleuthero tincture (300mg plant extract equivalent) in two divided doses of 2mL in the morning and PM. Time to exhaustion was 5.4% greater in placebo and 16.3% greater with eleuthero.
Despite the above three trials, one review conluded no significant effects associated with eleuthero due to the aforementioned studies being low in methodological quality and other trials of higher quality showing no effects. Two trials using ENDUROX (brand name) failed to find any influence on heart rate or fat oxidation during submaximal exercise (800mg eleuthero leaf) and no influence on fat oxidation or oxygen consumption with 1200mg eleuthero leaf extract, respectively. One study (not located online; McNaughton et al.) failed to find an effect with 1000mg of the root extract failed to find an effect on VO2 max or grip strength (instead noting an increase in pectoral and leg strength by 15% and 13%) while the other studies noted that 3.4mL of eleuthero root extract tincture failed to find a significant influence on fat oxidation and oxygen consumption and 1,200mg of the leaf extract has also failed again during submaximal exercise.
Evidence is mixed currently, and conclusions are hard to draw as although the studies suggesting promise with eleuthero supplementation are less statistically robust (poor metholody and sample sizes) other more well controlled studies seem to evaluate submaximal exercise more, whereas the promising studies were in regards to anti-fatigue effects during maximal exercise
At this moment in time, a clear performance enhancing effect of eleuthero is not present but performance enhancement cannot be ruled out yet
8.3. Exercise-induced Immunosuppression
Eleuthero (cortex at 1g/kg bodyweight in mice for nine days) has been noted to suppress exercise-induced corticosterone increases to a similar degree as the active control of red Panax ginseng and some increases have been noted in Natural Killer cell activity, although for the latter it was unreliable (two of five tested herb samples abolished the decrease seen with exercise) and did not appear to be related to the Eleutheroside B and E content.
One study noted that consumption of eleuthero in humans (Taiga Wurzel at 25 drops daily, amount of bioactives unknown but the tincture being a 1:1 35% ethanolic extract or the root) increasing spontaneous and LF-7 induced blastic transformation of lymphocytes (no influence on esterase positive lymphocytes) and this T-cell stimulatory effect has been noted elsewhere when exercise was not a factor.
Unclear effects on exercise-induced immunosuppression. There appears to be a beneficial influence on circulating immune cells but no study has been conducted assessing the frequency of sickness in athletes
9Inflammation and Immunology
Several components in eleuthero have been noted to exert anti-inflammatory effects, such as isofraxidin (concentrations greater than 135µM in sarcoma cells) and the polysaccharide component (able to attenuate hepatic failure from combination D-galactosamine and LPS).
Other studies have noted reduction of inflammation as assessed by attenuating iNOS induction in microglia (via Nrf2 activation from CREB) and macrophages (via NF-kB inhibition secondary to inhibiting Akt/JNK pathways) in concentration dependent manners.
General anti-inflammatory properties, but currently insufficient evidence to suggest that they are of remarkable potency or unique in any way. The anti-inflammatory properties of eleuthero are not yet proven to me remarkable relative to other herbs
Ciwujianoside D1 has been noted to prevent mast cell degranulation and subsequent histamine release in a concentration-dependent manner with a potency reported to be 6800-fold more effective than the active control of disodium cromoglycate. A basic extract of eleuthero was able to inhibit allergic responses and mast cell degranulation in mice injected with compound 48/80 by 25% at the dose of 1g/kg and this dose inhibited passive cutaneous allergic reaction by 51%. Similar effects have been replicated with the stem extract.
May have some anti-allergic effects, but although they seen to be biologically relevant this topic is not well explored
9.3. Natural Killer Cells
One study in humans using eleuthero as a tincture (10mL thrice daily for 30mL daily, taken for 4 weeks) noted an increase in natural killer cells alongside increases in cytotoxic and helper T-cells.
An increase in the secretion of some interleukins (IL-1 and IL-6, but not IL-2) has been noted in rats with the whole root extract rather than isolated main two eleutherosides and this has been found with the whole ethanolic extract in vitro.
10Interactions with Hormones
Ingestion of 8mL of a 33% ethanolic extract of eleuthero root (equivalent to 4g root) in trained athletes prior to a training session was associated with an decrease in the testosterone:cortisol ratio (28.7%) due to nonsignificant trends to reduce testosterone (7%) and increase cortisol (31%).
One study suggested an augmentation, rather than reduction, in stress associated with 4g root equivalent of eleuthero taken in athletes prior to training
Eleutherococcus senticosus has failed to significantly modify prolactin levels in male rats over 15 days when treated with up to 100mg/kg in rats.
No significant influences on prolactin observed with eleuthero supplementation
A combination therapy of Astragalus membranaceus, eleuthero, and Phlomis umbrosa appears to have traditional usage to stimulate growth in children (Korean medicine). Previous studies in immature male and female rats have noted longitudinal bone growth with this combination therapy.
A subsequent study in female rats given either 100mg/kg of phytotherapy twice daily (200mg/kg total; ratios of 26.5:31.2:42.3 for Phlomis umbrosa, astragalus, and eleuthero) appeared to increase bone growth to a comparable degree as the active control of 20mcg/kg HGH injections daily; this was associated with a serum increase of IGF-1 increase of 11.7% relative to control with no changes in IGFBP-3 (its binding protein) detected at week 3.
No evidence for eleuthero in isolation on IGF-1, but combination therapy with two other herbs has once been shown to slightly increase IGF-1 levels in serum of adolescent rats
11Interactions with Organ Systems
Eleuthero has been reported to increase retinal sensitivity towards light.
500mg/kg eleuthero given orally for 12 weeks noted that in diabetic rats (but not control) that there is an induction in the activity of the antioxidant enzymes SOD (12.5%), glutathione peroxidase (11.8%), and catalase (36%) relative to control which was met with partial normalization of radicals in the cytosol and improved membrane fluidity.
Decreases in hepatic lipid peroxidation from exercise have been noted (12% reduction with 170mg/kg in mice).
6 months supplementation of eleuthero in postmenopausal women failed to note a significant adverse effect on hepatic enzymes in serum and 800mg for 8 weeks in athletes also failed to modify serum liver enzymes.
In flies (Drosophila melanogaster), the addition of eleuthero to the feed was able to promote survival after ingsestion of bacteria that were toxic to the intestines, with the fruit (92.2%) outperforming root extracts (78.8%; control below 40%). The observed effects were thought to be due to inducing expression of antimicrobial peptides in the intestines (occurred with fruits, but not roots) and preventing histological changes to the intestines.
12Interactions with Disease States
12.1. Chronic Fatigue Syndrome
One study has been conducted assessing the efficacy of eleuthero failed to find any overall significant differences between eleuthero and placebo in reducing fatigue over 2 months of treatment with 2g of eleutherococcus with 0.112% eleutherosides B plus E. As the treatment group differed slightly at baseline (a greater percentage of persons reporting more severe fatigue) a subgroup analysis was conducted and this dose of siberian ginseng was found effective for the people with less drastic fatigue, and still ineffective for the more exacerbated fatigue.
Minimal evidence to support the usage of eleuthero in chronic fatigue syndrome, may be able to help those with minor symptoms but more research would be needed to confirm
Adapt-232 is a mixture of eleutherococcus senticosus alongside Rhodiola Rosea and Schisandra chinensis and appears to be somewhat tested in regards to its efficacy.
In neuroblastoma cells (T98G) testing for isolated compounds in the three herbs noted that there were more overall genes activated at 300mcg/mL (practical relevance of these activations unknown) with the combination than with isolated compounds; the researchers hypothesized that the influence on these depended on synergy.
13.2. Scutellaria baicalensis
In nasal fluid incubated with either Scutellaria baicalensis alone or in combination with eleuthero root extract was able to exert anti-allergic effects in nasal cells as assessed by anti-IgE induced mast cell degranulation; despite eleuthero having no inherent effect, it potentiated the effects of scutellaria reducing the required concentration for maximal suppression from 20μg/mL to 0.2μg/mL of each herb. An anti-allergic effect was seen when assessing cytokine levels (IFN-γ, IL-5, IL-1β, and TNF-α) where 2μg/mL of both agents which outperformed the active control of fluticasone propionate.
Eleuthero may be synergistic with scutellaria in regards to reducing inflammation and mast cell degranulation (preventing allergic reactions)
The acute LD50 for the dried roots of eleuthero appears to be greater than 3g/kg in mice when looking at the water extract (equivalent of 25g/kg of the dry root) and the LD50 for a 33% ethanolic extract appears to be 22.7mL/kg (death associated with neural and respiratory depression) which the authors attributed to the Alcohol itself.