Oxycodone

opioid analgesic, full mu-receptor agonist

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Oxycodone has no classical depletion machinery. It is metabolized by CYP3A4 and CYP2D6 as a substrate, is excreted largely as the parent drug and conjugates in urine, and the Roxicodone label (read through a summarizing tool) contains no mention of any vitamin, mineral, sodium, calcium, iron, copper or bone effect [1]. The real signals are hormonal, not dietary. The one grade above yellow is an endocrine effect: men on long-term daily oxycodone have lower testosterone and higher odds of androgen deficiency than men on hydrocodone, and a placebo-controlled study showed a larger testosterone fall on controlled-release oxycodone than on placebo [3][5]. Under Hard Rule 2 this is a drug effect on a hormone axis, not a nutrient deficiency, and it is labeled that way throughout. It is graded orange, bounded to men on long-term daily use, because the evidence is observational or exploratory and the comparator in the largest study is another opioid.

opioid analgesic, full mu-receptor agonist · ATC N02AA05 (WHO ATC/DDD Index [2]) · reviewed 2026-10-06. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Oxycodone in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe: Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

Testosterone and the androgen axis: men on long-term daily use, dose-related (hormone suppression, not a nutrient deficiency)

Orange — Moderate

See study details

In men on daily oxycodone for chronic pain, androgen deficiency is more likely than with hydrocodone, and testosterone fell more on controlled-release oxycodone than on placebo. This is a drug effect on the hypothalamic-pituitary-gonadal axis, not a dietary shortfall.

Full detail and limits

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. Orange

Limits on what this shows

Null findings: In Rubinstein 2013, daily dose was not significantly associated with hypogonadism [4]. In the oxycodone dose analysis the per-10 mg odds are close to 1 [3]. In Lamprecht 2018 (40 long-term oral or transdermal opioid users, opioids not named in the retrieved abstract), testosterone in men was inversely associated with BMI but not with opioid use, with only a non-significant trend to low testosterone [9].
At-risk subgroups: Men on daily therapy beyond about 3 months; users of long-acting or controlled-release forms (the 2013 comparison); higher BMI (an independent correlate). Women: the label lists amenorrhea [1], but no oxycodone-specific female hormone measurement was retrieved.

Direction

Hormone suppression (endocrine effect). Hard Rule 2: low testosterone is the drug's own pharmacologic effect, not a nutrient deficiency, and no intake change is implied.

Regulatory status

Roxicodone label 12.2: extended opioid use may influence the hypothalamic-pituitary-gonadal axis, potentially resulting in androgen deficiency (low libido, impotence, erectile dysfunction, amenorrhea or infertility); opioids inhibit LH secretion. Section 6.2 postmarketing: cases of androgen deficiency with opioid use for an extended period [1].

Population evidence

Rubinstein 2017 [3]: retrospective cohort, 1,159 men aged 18 to 80 on a stable single opioid for chronic non-cancer pain for at least 90 days in one integrated health system; morning total testosterone; logistic regression adjusted for dose, obesity, age, hypertension, hyperlipidemia and diabetes, hydrocodone as referent. Oxycodone OR 3.15 (95% CI 1.87 to 5.33) for androgen deficiency versus hydrocodone (methadone OR 7.33; fentanyl OR 25.7). Per 10 mg dose increase: hydrocodone OR 1.18 (1.09 to 1.28), oxycodone OR 1.01 (1.00 to 1.02). Eichenbaum 2015 [5]: study 3, randomized double-blind placebo-controlled, osteoarthritis patients; mean change in total testosterone from baseline: oxycodone controlled-release 20 mg -2.7 (0.93) nmol/L, placebo -0.3 (1.62), tapentadol ER 100 mg -1.9 and 200 mg -2.1 (values and bracketed spread as reported; spread type and sample size not captured). Rubinstein 2013 [4]: 81 men, 53% hypogonadal (morning total testosterone below 250 ng/dL); 74% (34/46) on long-acting versus 34% (12/35) on short-acting opioids (hydrocodone or oxycodone); odds 4.78 times higher for long-acting. Ray 2017 [6]: exploratory, free testosterone by equilibrium dialysis and LC-MS/MS, lower in the hydrocodone, oxycodone and morphine group than in controls (p=0.0253); oxycodone not analyzed alone in the retrieved abstract.

Mechanism

Present and named. Opioids inhibit LH secretion (label 12.2 [1]); a 2025 review attributes the effect mainly to inhibition of GnRH synthesis and secretion, with prevalence of 20 to 80% in affected men depending on opioid, duration, age and threshold [7]. In vitro, oxycodone weakly inhibited placental aromatase (Ki about 92 micromolar, listing summary) [8]; this concerns estrogen formation, is far from clinical exposure and is not used for grading.

Why orange, not red

The oxycodone-specific odds ratio is against hydrocodone, which is itself an opioid associated with suppression, so it does not test oxycodone against non-use. The placebo-controlled arm is controlled-release oxycodone, not plain immediate-release, in an exploratory analysis whose authors state it is not for decision making. [3] and [4] come from the same health system.

Counter-evidence held on record

Counter-evidence and confounding Confounding by indication is presumed: chronic pain, obesity, age and comorbidity independently lower testosterone, and Rubinstein adjusted for several but not all of them [3]. [3] and [4] share a health system. The Eichenbaum study was designed to test tapentadol, with oxycodone as the comparator, and was read from the abstract only [5]. The large prevalence range in the review is not stratified by oxycodone [7]. Framing caution This is a hormone-axis effect of long-term use in men, not a nutrient deficiency. Do not suggest zinc, vitamin D or herbal testosterone products from this entry. Evaluation and any treatment belong to a prescriber.

Adrenal insufficiency, HPA suppression: class extrapolation, hormone not a nutrient

Yellow — Low

See study details

The oxycodone label lists adrenal insufficiency as an opioid class event, and cohort studies of long-term opioid users find secondary adrenal insufficiency, but none of the retrieved cohorts names oxycodone.

Full detail and limits

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow

Limits on what this shows

Null findings: A single oral oxycodone 20 mg dose in healthy adults (30 given oxycodone, 19 controls) was followed by higher cortisol in carriers of certain IL1B alleles, i.e. acute HPA activation, not suppression (PubMed listing summary; abstract not retrievable) [11]. A listing summary of a 2022 reappraisal reports an opioid-associated insufficiency prevalence of 4.0% with a cortisol cutoff below 405 nmol/L versus 19% with a traditional 500 nmol/L cutoff, so prevalence depends on assay and threshold [27].
At-risk subgroups: People on opioids for more than a month (label), and higher morphine-equivalent daily dose [9].

Direction

Hormone suppression (cortisol axis). Hard Rule 2: an endocrine adverse effect, not a nutrient depletion.

Regulatory status

Label 5.9 and 6.2: "Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use," with presentation including nausea, vomiting, anorexia, fatigue, weakness, dizziness and low blood pressure. Label 12.2: opioids inhibit ACTH and cortisol secretion in humans [1].

Population evidence

Lamprecht 2018 [9]: cross-sectional, 40 long-term oral or transdermal opioid users versus 25 controls; secondary adrenal insufficiency on a failed stimulation test in 22.5% of users versus none of the controls (P=0.01); users with insufficiency had higher median morphine-equivalent daily dose (P=0.037). Gibb 2016 [10]: cross-sectional, 48 chronic pain patients on long-term opioids; the retrieved abstract text concluded the axis is suppressed in a clinically significant proportion (a PubMed listing summary gave 8.3% with morning cortisol below 100 nmol/L). A Mayo Clinic Proceedings review reports 9 to 29% in long-term opioid therapy (listing summary) [12]. Neither primary abstract names oxycodone.

Mechanism

Present: opioid-mediated suppression of ACTH release (label 12.2 [1]).

Class cohort test

CLASS EXTRAPOLATION. Oxycodone was not confirmed in the cohort of [9], [10], [12] or [27]; their abstracts do not name the opioids. Capped at yellow. The only oxycodone-named human cortisol data are acute dosing, which points the other way [11]. No hydrocodone data were borrowed.

Counter-evidence held on record

Counter-evidence and confounding Small cross-sectional studies, no non-opioid pain comparator, and obesity and age correlate with cortisol [10]. The cohorts were long-term opioid users, not short-course patients, and acute versus chronic time course differs [11]. Framing caution This is a symptom-triggered clinical awareness prompt for people on opioids beyond a month, not a nutrient claim. It does not imply any supplement.

Hyponatremia: dilutional or retention risk, class mechanism only, no oxycodone-attributed case found

Yellow — Low

See study details

The label states that opioids induce antidiuretic hormone release, which makes a water-retention (dilutional) low sodium plausible, but no oxycodone-attributed case or cohort was found.

Full detail and limits

Limits on what this shows

Null findings: The oxycodone co-medication cases resolved after the anticonvulsant was withdrawn with oxycodone continued, which argues against oxycodone as the cause in those patients [14].
At-risk subgroups: People also taking diuretics or other SIADH-associated drugs; older adults.

Direction

Retention or dilution (excess water relative to sodium). This is not a dietary sodium deficiency, and added salt or sodium intake is not the remedy (Hard Rule 5).

Regulatory status

Label section 7 (word search through a summarizer): "Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone." The words hyponatremia, SIADH and sodium do not appear in the label text searched [1].

Population evidence

None for oxycodone. A 2021 review of drug-induced SIADH lists opioid analgesics among causative drug classes without naming oxycodone or giving effect sizes (listing summary) [13]. A PubMed search for oxycodone with hyponatremia or SIADH returned only two case reports in which oxycodone was a co-medication: a 78-year-old on oxycodone/naloxone whose sodium fell to 127 mmol/L and recovered to 143 mmol/L after oxcarbazepine was stopped, and a carbamazepine case; both were attributed to the anticonvulsant [14].

Mechanism

Present as a statement: opioid-induced ADH release (label). Its magnitude for oxycodone was not measured in any retrieved source.

Class cohort test

CLASS EXTRAPOLATION. Oxycodone was not in any retrieved hyponatremia cohort; the support is a label mechanism sentence for opioids as a class plus a narrative review. Capped at yellow.

Counter-evidence held on record

Counter-evidence and confounding Confounding by indication is presumed (Hard Rule 6): the conditions treated with opioids and the co-medications can lower sodium independently, and no retrieved source separates these from oxycodone. Framing caution This is a possible water-retention effect, not a sodium shortfall. Supplementing salt would be the hazard, not the remedy. Serum sodium is a monitoring prompt only.

Vitamin D: context flag, reverse direction, confounding by indication

Yellow — Low

See study details

No retrieved study shows oxycodone lowers 25-hydroxyvitamin D. The observational association runs from low vitamin D to higher opioid use, so this is a context flag, not a drug-caused deficiency.

Full detail and limits

Limits on what this shows

Null findings: No oxycodone study with measured 25(OH)D was located, so there is no direct null either.
At-risk subgroups: Not defined from oxycodone data.

Direction

Reverse or timing relationship (nutrient status relating to opioid use or response, not the drug lowering the nutrient). Hard Rule 4.

Regulatory status

The words vitamin, calcium, bone and osteoporosis do not appear in the label text searched [1].

Population evidence

Helde-Frankling and Bjorkhem-Bergman 2017 [15]: review in which low vitamin D levels were associated in observational studies with more pain and higher opioid doses; opioids not named (listing summary). Kemeny 2021 [16]: increased prevalence of vitamin D deficiency in patients with opioid use disorder and an inverse, dose-dependent association of vitamin D level with self-reported opioid use; in mouse models vitamin D deficiency amplified opioid responses (listing summary; no 25(OH)D values or ORs in the abstract). Neither study is in an oxycodone-treated pain cohort.

Mechanism

No direct mechanism by which oxycodone lowers vitamin D was found. An indirect route (hypogonadism, reduced mobility or indoor time in chronic pain) is a hypothesis not tested in retrieved sources. BMD and fracture are outcomes, not vitamin D deficiency (Hard Rule 2); a PubMed search for oxycodone with bone density, osteoporosis and fracture returned only an unrelated mastocytosis case report.

Class cohort test

CLASS EXTRAPOLATION and context. Oxycodone not named in [15] or [16]. Confounding by indication is presumed (Hard Rule 6): chronic pain populations may already be low in vitamin D before opioid therapy. Capped at yellow.

Counter-evidence held on record

Counter-evidence and confounding Low vitamin D may drive pain and higher opioid use rather than the reverse [15][16]. No baseline-versus-on-treatment comparison exists for oxycodone, so Hard Rule 6 cannot be excluded. Framing caution Do not present this as oxycodone causing vitamin D deficiency. If vitamin D is checked, the reason is general risk factors, and no dose is recommended here.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden: in vitro and animal data, mixed direction, no human data

Yellow — Low

See study details

Oxycodone reduced cell viability in mitochondrial-activity assays in four cell cultures and is linked to mitochondrial changes in perinatal rat models, but stabilized mitochondrial membrane potential in ischemia-reperfusion models.

Full detail and limits

Limits on what this shows

Null findings: No study measured mitochondrial function in people taking oxycodone.
At-risk subgroups: Not defined; perinatal exposure is an animal finding only.

Direction

Mixed and model-dependent: adverse in cultured cells and perinatal exposure, protective in ischemia-reperfusion. Not a nutrient entry.

Regulatory status

No mitochondrial mention in the label text searched [1].

Population evidence

Nylander 2024 [22]: six opioids including oxycodone tested in primary cortical cells, SH-SY5Y cells and differentiated and undifferentiated NG108-15 cells; MTT assay (mitochondrial activity) and lactate dehydrogenase leakage; reduced viability across cultures, methadone most toxic, morphine least, oxycodone intermediate; concentrations not captured. Jiang 2025 [23]: rat ischemia-reperfusion and H9c2 cell model; oxycodone reduced LDH release and ROS and maintained mitochondrial membrane integrity via AMPK, SIRT1 and PGC-1 alpha. Flores 2024 [24] and Gowen 2023 [25] (listing summaries): perinatal oxycodone exposure in rats associated with mitochondrial and synaptic dysfunction in cortical synaptosomes. Yu 2020 [26] (listing summary): mitochondria-mediated caspase activity and oxidative damage in low-EGFR cancer cell lines.

Mechanism

Named only in the protective setting (AMPK/SIRT1/PGC-1 alpha activation [23]). Mechanism of the toxic findings was not captured.

Counter-evidence held on record

Counter-evidence and confounding Culture concentrations are unlikely to match clinical plasma levels, MTT is a surrogate, and the protective and toxic findings cannot be reconciled without dose data. Several records were read as PubMed listing summaries only. Framing caution Preclinical signal only. It should not be presented to consumers as mitochondrial damage or as a reason to take mitochondrial supplements.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress: in vitro and animal data, mixed and reverse direction

Yellow — Low

See study details

Oxycodone lowered ROS in two ischemia-reperfusion style models and raised macrophage ROS in mice, with no human redox marker data.

Full detail and limits

Limits on what this shows

Null findings: No human study measuring oxidative markers during oxycodone use was retrieved.
At-risk subgroups: Not defined.

Direction

Mixed. Protective (reverse) in ischemia models [23][26]; pro-oxidant in mouse macrophages and in low-EGFR cancer cells.

Regulatory status

The words oxidative and antioxidant do not appear in the label text searched [1].

Population evidence

Jiang 2025 [23]: oxycodone suppressed ROS and LDH release in rat and H9c2 ischemia-reperfusion models. Kong 2019 (listing summary) [29]: in fetal hippocampal neurons under oxygen-glucose deprivation, oxycodone inhibited ROS production through kappa and delta opioid receptors. Kozlowski 2017 and Filipczak-Bryniarska 2018 (listing summaries) [30]: in mice, opioids including oxycodone enhanced macrophage reactive oxygen intermediate and nitric oxide production, with oxycodone among the weakest immunomodulators. Yu 2020 [26]: oxidative stress and damage in low-EGFR cancer cell lines.

Mechanism

Present only in the protective setting (receptor-mediated and AMPK-linked). No glutathione, MDA or antioxidant-enzyme data in humans were found.

Counter-evidence held on record

Counter-evidence and confounding Intraperitoneal macrophage assays, ischemia models and cancer cell lines are not comparable and none reflects oral therapeutic exposure. Several records were read as listing summaries. Framing caution Mixed preclinical data. Not an oxidative-stress deficiency claim and not a reason for antioxidant supplements.

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Copper: class extrapolation from heroin and methadone populations, possible retention direction, not depletion

Yellow — Low

See study details

No study measured copper in people taking oxycodone. A review of zinc and opioids reports higher plasma copper in heroin-addicted patients and lower urinary copper elimination under methadone maintenance, which is class-level context only and runs toward retention, not depletion.

Full detail and limits

Limits on what this shows

Null findings: No oxycodone study with serum copper, ceruloplasmin or urinary copper was located. A trace-element study of drug-dependent subjects (Cu, Zn, Fe; PMC1872021) appeared in search results but was blocked by a bot challenge and was not opened, so its drugs and results are unknown.
At-risk subgroups: Not defined for oxycodone.

Direction

Possible retention or elevation (higher plasma and red-cell copper in heroin users; reduced urinary copper excretion on methadone), reported in the review as accompanying low zinc. This is not a copper shortfall. Hard Rule 5: if real, the risk is excess or retention, and copper supplementation would be the hazard, not the remedy.

Regulatory status

Word search of the Roxicodone label for copper: absent [1].

Population evidence

Ciubotariu 2015 [31], a narrative review of zinc-opioid interactions (human, animal and in vitro work through April 2015), opened as full text through a summarizing tool. Under "Human studies" it states "low zinc plasma is accompanied by low intraerythrocytic zinc and by increased plasma and intraerythrocytic copper" in heroin-addicted patients (citing Ruiz Martinez 1990, Klin Wochenschr 68:507-11) and "copper urinary elimination is decreased under methadone maintenance treatment" (citing Iyengar 1994, J Trace Elem Electrolytes Health Dis 8:213-5). Both primary papers were NOT opened; sample sizes, effect sizes and comparators were not captured. Oxycodone does not appear anywhere in the review text.

Mechanism

Not established. The review links the findings to opioid-associated zinc misbalance; no mechanism for oxycodone and copper was found.

Class cohort test

CLASS EXTRAPOLATION. Oxycodone was NOT in the cohort of any source behind this entry; the data concern heroin users and methadone patients (illicit-drug and opioid-dependence populations). Tier C, capped at yellow. No hydrocodone data were borrowed.

Counter-evidence held on record

Counter-evidence and confounding Confounding by indication and population is presumed (Hard Rule 6): illicit drug use, hepatitis, diet, lifestyle and addiction treatment can alter plasma copper independently, and these are small older studies read only through a secondary review. Plasma copper also rises with inflammation. Extrapolation to prescribed oral oxycodone for pain is unsupported. Framing caution Not a copper deficiency claim and not a reason to take copper or zinc supplements. Excess copper is the direction suggested, so supplementation is the hazard. Context flag only.

Iron

Not graded — disclosed evidence gap

See study details

No evidence was found that oxycodone alters iron absorption, stores or iron-deficiency risk.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

Why no grade: Dual condition met: no Tier B or C iron evidence for oxycodone, and no circulating claim found to rebut. Mixed result: a genuine absence in the records opened, with tooling limits (bot-challenged PMC pages, 429 on listing and search endpoints) and no traced consumer claim for oxycodone and iron. Re-check recommended. Not a finding of safety.

What was searched

PubMed listing "oxycodone anemia" (25 records; all co-medication contexts, mostly sickle cell disease, one hemolytic case reported under Oxygen delivery); "oxycodone iron copper" (404, no records as interpreted); "oxycodone hemoglobin anemia iron" and "oxycodone iron deficiency anemia hemoglobin" (rate-limited, not read). Label word search for iron: absent [1]. A triple opioid receptor knockout mouse paper reporting iron deficiency and anemia appeared in the listing but is a receptor-deletion model without oxycodone exposure and is not used.

Repair-pass searches

WebSearch queries (standard and extended): "oxycodone iron deficiency anemia ferritin opioid"; "oxycodone hemoglobin iron deficiency copper levels patients"; "oxycodone use associated with low ferritin OR iron deficiency OR anemia cohort"; "opioid analgesics iron absorption anemia mechanism oxycodone hepcidin"; "Zeilfelder Cell Systems 2025 hepcidin drug screen painkillers oxycodone". Opened and excluded: Zeilfelder 2025 [34] (hepcidin rise in liver cancer cells with diclofenac and acetaminophen; full text states no opioid was tested); Ergelen 2025 [35] (129 patients with opioid use disorder, buprenorphine/naloxone; oxycodone not named; no iron or ferritin values in the abstract). A retrospective study of chronic opioid use and hematological markers (PMC9290418) was blocked by a bot challenge and not opened. A BBRC 2020 paper on oxycodone and hematopoietic progenitors was seen only as a search-result title (robots-disallowed, not opened) and concerns progenitor stimulation, not iron. Consumer pages found (an opioid-anemia blog) are Tier D and not used. A PubMed "oxycodone ferritin" listing returned 429 and was not retried.

Channel outcomes

Original review: as for Copper (PubMed listings intermittent, article pages and Europe PMC blocked, two iron-and-hemoglobin listing queries rate-limited). Repair pass: WebSearch worked; PubMed listing, OpenAlex search and Crossref search returned 429.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk: rodent data with one null, no human oxycodone-specific study

Yellow — Low

See study details

Oxycodone altered gut bacterial composition in several rodent studies, one rat study reported no effect, and human opioid microbiome data do not name oxycodone.

Full detail and limits

Limits on what this shows

Null findings: Inan 2024 [19]: in rats given chronic oxycodone for 12 days, the PubMed listing summary states oxycodone "did not affect gut microbiome and integrity"; the abstract itself could not be retrieved. In [17], alpha diversity was not changed by oxycodone.
At-risk subgroups: Not defined from human oxycodone data.

Direction

Composition change (neither depletion nor excess of a nutrient). Findings are model-specific and not shown to cause a deficiency.

Regulatory status

No microbiome mention found in the label text searched. Label lists constipation as a common adverse reaction (3% or more) and 12.2 describes reduced GI motility [1].

Population evidence

Duffy 2026 [17]: two rat strains self-administering oxycodone or saline; alpha diversity differed by strain, not by oxycodone; 15 taxa differed between oxycodone and saline groups. Kesh 2024 [18]: mice given morphine and/or oxycodone over 10 weeks of caerulein-induced chronic pancreatitis; significant changes in fecal bacterial composition versus controls, and fecal transplant into germ-free mice transferred the inflammatory and pain phenotype (morphine and oxycodone groups reported together in the retrieved abstract). Tao 2026 preprint [20] (listing summary): 3 days of oxycodone in mice, disruption persisting to day 70 with Akkermansia and Marvinbryantia enriched and Eubacterium_xylanophilum depleted; not peer reviewed. Lyu 2022 [20] (listing summary): developmental exposure altered adult microbiota in mice.

Mechanism

Plausible, not demonstrated for oxycodone: reduced motility and constipation could change the gut environment; opioid effects on the gut barrier were proposed in the rodent work.

Class cohort test

CLASS EXTRAPOLATION for the human claim only. Acharya 2017 [21] (chronic opioid users with cirrhosis; 72 users matched with 72 non-users; dysbiosis with lower autochthonous taxa) does not name oxycodone in the retrieved summary, so it is Tier C. Rodent studies [17][18][20] name oxycodone as the exposure and are Tier B for this drug. Capped at yellow.

Counter-evidence held on record

Counter-evidence and confounding Rodent doses and self-administration patterns differ from oral prescribing; the cirrhosis population limits generalizability [21]; diet, laxative use and constipation are plausible confounders of any human comparison. Framing caution This is not a claim of dysbiosis in patients taking oxycodone and not a reason for probiotics or supplements.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

Oxygen delivery/utilization: single case report in a misuse route, outcome only

Yellow — Low

See study details

One case report links injection of crushed long-acting opioid tablets, indexed as oxycodone, to thrombotic microangiopathy with hemolytic anemia that resolved on stopping. This is an outcome in a misuse setting, not an oxygen-delivery nutrient finding.

Full detail and limits

Limits on what this shows

Null findings: A PubMed search for oxycodone with anemia returned 25 records, all with oxycodone as a co-medication, mostly in sickle cell disease where anemia is the underlying condition; none measured hemoglobin as an outcome of oxycodone use. A PubMed-listed oxymorphone case (PMID 28718268) was not opened and is not borrowed.
At-risk subgroups: People who crush and inject extended-release tablets. Not applicable to oral use as prescribed.

Direction

Outcome (hemolytic anemia and low platelets). Hard Rule 2: anemia is not iron deficiency and no nutrient was measured.

Regulatory status

Label adverse reactions list "anemia, leukopenia" under blood and lymphatic disorders (word search via summarizer); methemoglobin and hemolysis do not appear [1]. Label respiratory depression is the drug's own hypoventilation effect and is not an oxygen-delivery deficiency; it is not graded here.

Population evidence

Di 2018 [28]: single case, 43-year-old man with chronic hepatitis C, diabetes and polysubstance use, thrombocytopenia and microangiopathic hemolytic anemia with schistocytes; thrombotic thrombocytopenic purpura and other causes excluded; he was crushing long-acting opioid pills for injection; hemolysis and platelet counts recovered on discontinuation. The abstract text I read says "long-acting opioid"; the identification as oxycodone comes from the summarizing tool and PubMed indexing.

Mechanism

Not established. Whether the cause is oxycodone itself, tablet excipients or the injection route cannot be separated from the abstract.

Counter-evidence held on record

Counter-evidence and confounding A single case with multiple comorbidities; no replication. Does not support any effect of oral therapeutic use. Framing caution Not a consumer deficiency claim and not an indication to take iron or other supplements.

ATP production

Not graded — disclosed evidence gap

See study details

No study measured cellular ATP or oxidative phosphorylation output with oxycodone exposure.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

Why no grade: Dual condition met: no Tier B or C evidence of an ATP effect, and no circulating claim found to rebut. Partly tooling-limited (eight undisplayed listing records, 429 on listing and search endpoints on retry, no traced consumer claim). Membrane-potential data are surrogate markers and are carried only under Mitochondrial burden. The mitochondrial findings are carried in the Mitochondrial burden entry and are not counted again here. Not a finding of safety.

What was searched

PubMed listing "oxycodone ATP" (26 records; records 1 to 18 were transporter, pharmacogenetic and receptor papers where ATP appears only as ATP-binding cassette or ATPase; records 19 to 26 were not displayed by the summarizer). "oxycodone ATP oxidative phosphorylation respiration" returned 404 (no records, as interpreted). The mitochondrial listing (see Mitochondrial burden) returned MTT viability and AMPK findings but no ATP, respiration or membrane-potential-linked energy measurement in the abstracts read. Jiang 2025 reports AMPK activation, which is an energy-sensing pathway, not an ATP measurement [23].

Repair-pass searches

WebSearch queries: "oxycodone mitochondrial respiration ATP oxidative phosphorylation"; "oxycodone mitochondrial function ATP content cells study" (domain-restricted to PubMed, PMC, MDPI, Frontiers, Springer, ScienceDirect); "oxycodone brain mitochondria oxygen consumption rate respiration ATP synthesis rat"; "oxycodone bioenergetics ATP levels decreased cells neurons cardiomyocytes". Opened and checked for ATP, oxygen consumption or respiration: Jiang 2025 [23] full text on PMC (measured JC-10 membrane potential, ROS, MDA, LDH and AMPK signaling; no ATP content, no respiration); Liu 2025 [32] (oxycodone in LPS lung injury, mitophagy markers, mitochondrial DNA copy number and mitochondrial ROS; no ATP, no oxygen consumption, no membrane potential); Zhao 2020 [33] (oxycodone in rat cardiac ischemia-reperfusion, PI3K/Akt; no ATP or energy-metabolism measurement). Respirometry papers returned by search (rat and pig brain mitochondria methods) do not involve oxycodone. A fentanyl hepatocyte study (mitochondrial ATP-sensitive K+ channels) was seen as a title only and is another drug. A PubMed listing for "oxycodone ATP mitochondrial respiration" and OpenAlex and Crossref search queries returned 429 and were not retried.

Channel outcomes

Original review: PubMed listings opened with a summarizing tool; article pages and Europe PMC not accessible; eight records not displayed. Repair pass: WebSearch and single PubMed article pages worked; listing and search endpoints returned 429.

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

Constipation as a nutrient problem (fiber, fluid or mineral depletion)
Where it comes from: The batch brief rationale for this drug lists chronic constipation under the nutrient angles. Origin on a consumer page not traced.
Why it fails: Constipation is a labeled adverse reaction (3% or more) and the drug's own effect on GI motility [1]. It is an outcome, not a nutrient measurement, so Hard Rule 2 bars filing it as a deficiency. No source retrieved shows a nutrient fall caused by oxycodone constipation. It is carried only as context in the Gut microbiome entry.

How the body handles this medication

Metabolism and enzymes: N-dealkylation to noroxycodone (the major circulating metabolite) is catalyzed by CYP3A4; CYP2D6 forms oxymorphone by O-demethylation. Oxycodone is a substrate of these enzymes. No CYP induction or inhibition by oxycodone itself is described in the label sections retrieved.[1] Roxicodone label, 12.3, read via summarizer
Absorption: Oral bioavailability 60 to 87% (lower first-pass loss than many opioids). Steady state in about 18 to 24 hours. Food raised AUC by about 27% and delayed Tmax from about 1.25 to 2.54 hours in the label text as summarized. No named absorption transporter appears in the retrieved sections.[1] 12.3
Distribution: Volume of distribution at steady state 2.6 L/kg. Plasma protein binding about 45% at 37 C and pH 7.4.[1] 12.3
Elimination: Half-life 3.5 to 4 hours for the immediate-release tablet. Urinary recovery includes free oxycodone up to 19%, conjugated oxycodone up to 50% and conjugated oxymorphone up to 14%; free oxymorphone 0%.[1] 12.3
Renal and hepatic impairment: Exposure may rise because of reduced clearance. The label directs a lower than usual starting dosage in hepatic impairment (8.6) and gives similar guidance for renal impairment (8.7). Exposure fold-changes were not captured.[1] sections 8.6, 8.7, 12.3 (summarized)
Interactions, renal handling and food or mineral effects: CYP3A4 inhibitors (macrolides, azoles, protease inhibitors) and inducers (rifampin, carbamazepine, phenytoin) change oxycodone exposure. The label states that opioids can reduce the efficacy of diuretics by inducing antidiuretic hormone release; this is the only renal water-handling statement found. Label 12.2: opioids inhibit ACTH, cortisol and LH secretion. No vitamin, mineral, calcium, magnesium, iron, copper or sodium interaction was found by word search of the label.[1] sections 7 and 12.2, word search via summarizer

What the research says is worth watching

General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.

Lab / men on long-term use
Morning total testosterone
Worth considering for men on daily oxycodone beyond about 3 months who report low libido, erectile dysfunction, fatigue or reduced mood, drawn in the morning as in the cited cohorts and repeated if low [3][4]. This is a hormone-axis prompt, not a nutrient finding.
Symptoms / long-term use
Adrenal insufficiency awareness
Persistent nausea, vomiting, anorexia, fatigue, weakness, dizziness or low blood pressure on opioids beyond a month warrants a morning cortisol discussion with a prescriber, as the label notes [1]. Interpretation depends on assay and threshold [27].
Lab / conditional
Serum sodium
Only if confusion, nausea or new weakness occur, or if a diuretic, anticonvulsant such as oxcarbazepine or carbamazepine, or another SIADH-linked drug is co-prescribed [1][14]. A low result is a water-balance question, not a prompt to add salt.
Context
Vitamin D and bone
No oxycodone-specific reason to test was found. Testing follows general risk factors rather than oxycodone use. No dose is recommended here.
Interactions
CYP3A4 modifiers
Azole antifungals, macrolides, protease inhibitors, rifampin, carbamazepine and phenytoin change oxycodone exposure and are label matters for the prescriber [1]. No vitamin or mineral separation interval is listed in the label text searched. No supplement dose appears in this dossier, so no upper-limit comparison was needed.
Special populations
Pregnancy, renal, hepatic
The label carries a neonatal opioid withdrawal warning (section 5.4 title) and advises a lower starting dose in hepatic and renal impairment [1]. Perinatal mitochondrial and gut microbiome findings are rodent data only [17][20][24].

Overlap map, to prevent double counting

Testosterone and the androgen axis
Shares evidence with: Adrenal insufficiency
Note: Both rest on the same label sentence (12.2: opioids inhibit ACTH, cortisol and LH) and the same central opioid mechanism. They are two hormone axes, not independent confirmations of one another.
Testosterone (Rubinstein 2013 [4] and 2017 [3])
Shares evidence with: Itself
Note: Both come from the same Kaiser Permanente health system. Treat as one data source analyzed twice.
Testosterone
Shares evidence with: Vitamin D (context)
Note: Any bone-related claim would be a downstream outcome of the androgen effect, not a separate vitamin D finding. No shared study.
Adrenal insufficiency
Shares evidence with: Hyponatremia
Note: Both are hormone-mediated and could share a clinical presentation, but the evidence is separate: cohort data [9][10] versus one label ADH sentence [1].
Mitochondrial burden
Shares evidence with: Oxidative stress; ATP production (ungraded)
Note: Jiang 2025 [23] and Yu 2020 [26] support both the mitochondrial and oxidative entries. Count as one set of sources, not two. ATP is ungraded; [23], [32] and [33] were opened for it and contain no ATP measurement.
Gut microbiome risk
Shares evidence with: Fails verification: constipation
Note: The label constipation statement is cited in both as context; no independent microbiome evidence comes from it.
Oxygen delivery/utilization
Shares evidence with: Iron (ungraded)
Note: The hemolysis case [28] is the only anemia evidence and is not iron data. The oxygen entry is an outcome entry; iron remains a separate ungraded gap (Hard Rule 7).
Copper
Shares evidence with: Iron (ungraded)
Note: No shared source. [31] reports copper only (not iron) and the trace-element paper that may cover both was not opened. Separate entries per Hard Rule 7.

All references used above

Oxycodone

Findings for this medication

What the research found

Testosterone and the androgen axis: men on long-term daily use, dose-related (hormone suppression, not a nutrient deficiency)

Adrenal insufficiency, HPA suppression: class extrapolation, hormone not a nutrient

Hyponatremia: dilutional or retention risk, class mechanism only, no oxycodone-attributed case found

Vitamin D: context flag, reverse direction, confounding by indication

The five body-system areas

⚡Mitochondrial Burden

Mitochondrial burden: in vitro and animal data, mixed direction, no human data

💥Oxidative Stress

Oxidative stress: in vitro and animal data, mixed and reverse direction

⚖️Copper and Iron Balance

Copper: class extrapolation from heroin and methadone populations, possible retention direction, not depletion

Iron

🌿Gut Microbiome Risk

Gut microbiome risk: rodent data with one null, no human oxycodone-specific study

💨Oxygen and ATP Output

Oxygen delivery/utilization: single case report in a misuse route, outcome only

ATP production

Claims checked and not supported

Constipation as a nutrient problem (fiber, fluid or mineral depletion)

How the body handles this medication

What the research says is worth watching

Overlap map, to prevent double counting

Mitochondrial Burden

Oxidative Stress

Copper and Iron Balance

Gut Microbiome Risk

Oxygen and ATP Output