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Cited by 68Cardiovascular Health and Disease PreventionNitric Oxide and Endothelin EffectsCardiovascular and exercise physiology

Inorganic nitrite supplementation for healthy arterial aging

Open access
Sindler, Amy L., DeVan, Allison E., Fleenor, Bradley S., Seals, Douglas R.·2014·Journal of Applied Physiology
DOI 10.1152/japplphysiol.01100.2013PMC PMC3949212
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Abstract

Aging is the major risk factor for cardiovascular diseases (CVD). This is attributable primarily to adverse changes in arteries, notably, increases in large elastic artery stiffness and endothelial dysfunction mediated by inadequate concentrations of the vascular-protective molecule, nitric oxide (NO), and higher levels of oxidative stress and inflammation. Inorganic nitrite is a promising precursor molecule for augmenting circulating and tissue NO bioavailability because it requires only a one-step reduction to NO. Nitrite also acts as an independent signaling molecule, exerting many of the effects previously attributed to NO. Results of recent studies indicate that nitrite may be effective in the treatment of vascular aging. In old mice, short-term oral sodium nitrite supplementation reduces aortic pulse wave velocity, the gold-standard measure of large elastic artery stiffness, and ameliorates endothelial dysfunction, as indicated by normalization of NO-mediated endothelium-dependent dilation. These improvements in age-related vascular dysfunction with nitrite are mediated by reductions in oxidative stress and inflammation, and may be linked to increases in mitochondrial biogenesis and health. Increasing nitrite levels via dietary intake of nitrate appears to have similarly beneficial effects in many of the same physiological and clinical settings. Several clinical trials are being performed to determine the broad therapeutic potential of increasing nitrite bioavailability on human health and disease, including studies related to vascular aging. In summary, inorganic nitrite, as well as dietary nitrate supplementation, represents a promising therapy for treatment of arterial aging and prevention of age-associated CVD in humans.

AI snapshot

Written from the paper’s full text.

TL;DR

This synthesis article argues that inorganic nitrite, a one-step precursor to nitric oxide (NO), may treat arterial aging by reducing large elastic artery stiffness and endothelial dysfunction. It reviews preclinical mouse evidence and human trial data, concluding nitrite/nitrate supplementation is promising but chronic human outcome studies are still needed.

Key findings

  • Aging is the primary risk factor for cardiovascular disease, with arterial aging characterized by large elastic artery stiffness and vascular endothelial dysfunction driven by NO insufficiency, oxidative stress, and inflammation.
  • In old male C57/BL6 mice (26–28 mo vs. young 4–6 mo), oral sodium nitrite in drinking water (50 mg/l for 3 wk) restored plasma and arterial nitrite, reduced aortic pulse wave velocity, normalized NO-mediated endothelium-dependent dilation, normalized aortic advanced glycation end products, nitrotyrosine, superoxide, and NADPH oxidase (which was threefold greater in old aorta), and restored SOD activity (∼50% lower in old aorta).
  • Nitrite requires only a one-step reduction to NO, acts as an independent signaling molecule, and in some tissues can synthesize 10,000 times the amount of constitutive NO formation from NOS; dietary nitrate appears to have similarly beneficial effects in many settings.
  • Human evidence is mostly acute: sodium nitrite can mildly or moderately decrease blood pressure and increase forearm blood flow, but the effects of inorganic nitrite on arterial stiffness have not been investigated in humans; 4 wk of sodium nitrate decreased aortic pulse wave velocity in older adults with cardiovascular risk factors, and several clinical trials are ongoing.

Methods

  • Design: narrative synthesis/review of inorganic nitrite supplementation for arterial aging, integrating preclinical and clinical literature; not a systematic review or meta-analysis.
  • Data/sample: cited mouse studies used young (4–6 mo) and old (26–28 mo) male C57/BL6 mice with oral sodium nitrite (50 mg/l drinking water for 3 wk); Table 1 summarizes sodium nitrite administration in humans and nonhuman primates across acute and chronic doses and populations.
  • Analysis: qualitative mechanistic synthesis of arterial stiffness, endothelial function, oxidative stress, BH4/eNOS uncoupling, NADPH oxidase, SOD, inflammation, and mitochondrial function, with an integrative working hypothesis.

Limitations

  • Stated: much of the work to date has used preclinical models or acute administration in humans; more studies are needed to determine the broad therapeutic potential and feasibility of chronic nitrite or nitrate administration.
  • Stated: there is an absence of studies comparing the health benefits of nitrite vs. nitrate supplementation, and the effects of inorganic nitrite on arterial stiffness have not been investigated in humans.
  • Evident: as a synthesis article, it does not describe a systematic search, inclusion criteria, or risk-of-bias assessment; Table 1 notes wide-ranging doses, many acute studies, and some outcomes not reported or not significant.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1152/japplphysiol.01100.2013

Cites

207 of 207 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 177 cited sources checked · 0 supported · 0 flagged

  • Premisecitation
    § Abstract

    Most forms of cardiovascular disease are linked to dysfunction of arteries.

    “most forms of CVD are linked to dysfunction of arteries (59, 111).”
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    § Abstract

    Reduced nitric oxide bioavailability due to decreased endothelial nitric oxide synthase production, increased degradation, or both is the key mechanism mediating vascular endothelial dysfunction with aging.

    “Reduced bioavailability of NO as a result of decreased production by endothelial NO synthase (eNOS), increased degradation, or both, also is the key mechanism mediating vascular endothelial dysfunction with aging (118, 164, 177).”
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    § Abstract

    The key mechanism for reduced nitric oxide bioavailability with aging is oxidative stress.

    “The key mechanism for reduced NO bioavailability with aging is oxidative stress (49, 164, 177).”
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  • Premisecitation
    § Abstract

    Aging is the primary risk factor for cardiovascular diseases.

    “Aging is the major risk factor for cardiovascular diseases (CVD).”
    • Also stated in: § Abstract · plain
      “Aging is the primary risk factor for CVD, and therefore, most forms of CVD are diseases of aging (59, 98, 112, 136, 137).”
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  • Premisecitation
    § Abstract

    Sodium nitrite may show greater efficacy for increasing nitrite concentrations in some populations, as reported in older adults.

    “Sodium nitrite also may show greater efficacy for increasing nitrite concentrations in some populations, as has been reported in older adults (124).”
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    Premisecitation
    § Abstract

    Aging causes arterial dysfunction, which in turn leads to increased risk for cardiovascular disease.

    “Thus there is something about aging that causes dysfunction of arteries, which in turn, leads to an increased risk for CVD (100).”
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    Premisecitation
    § Abstract

    Structural factors in large elastic artery stiffening include increases in collagen and reductions in elastin.

    “Structural factors include changes to the extracellular matrix involving increases in collagen (fibrosis) and reductions in elastin (i.e., the major structural proteins in the arterial wall that confer stiffness and elasticity, respectively) (41).”
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    Premisecitation
    § Abstract

    Formation of advanced glycation end products increases with age and contributes to large elastic artery stiffening.

    “The formation of advanced glycation end products (AGEs), glucose-derived molecules that cross-link structural proteins in the arterial wall, also increases with age and contributes to large elastic artery stiffening (62).”
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    Premisecitation
    § Abstract

    Oxidative stress reduces nitric oxide bioavailability via excessive production of superoxide, which reacts with nitric oxide to form peroxynitrite.

    “Oxidative stress reduces NO bioavailability via excessive production of superoxide, which reacts with NO to form peroxynitrite.”
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    Premisecitation
    § Abstract

    Two key contributors to age-related arterial dysfunction are stiffening of the large elastic arteries and development of vascular endothelial dysfunction.

    “two key contributors are stiffening of the large elastic arteries (aorta and carotid arteries) and the development of vascular endothelial dysfunction (100, 142, 164, 194).”
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    Premisecitation
    § Abstract

    Large elastic artery stiffening with aging is mediated by changes in both structural and functional factors.

    “Large elastic artery stiffening with aging is mediated by changes in both structural and functional factors (99, 136, 195).”
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    § Abstract

    Vascular inflammation develops with aging and contributes to arterial dysfunction.

    “vascular inflammation develops with aging and also contributes to arterial dysfunction (34, 44, 108, 149, 186).”
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    Premisecitation
    § Abstract

    Mitochondrial dysfunction may play an important role in large elastic artery stiffening and endothelial dysfunction with aging via modulation of oxidative stress.

    “recent evidence suggests that mitochondrial dysfunction may play an important role in large elastic artery stiffening and endothelial dysfunction with aging via modulation of oxidative stress (33, 35, 56, 198).”
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    Premisecitation
    § Abstract

    Nitrite administration reduces skeletal muscle, renal, and liver injury after ischemia.

    “nitrite administration reduces skeletal muscle (188), renal (125, 179), and liver (46, 154, 169) injury after ischemia.”
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    Premisecitation
    § Abstract

    Reductions of nitrate to nitrite depend entirely on oral commensal bacteria, and individual differences in microflora may affect nitrate reduction.

    “reductions of nitrate to nitrite depend entirely on oral commensal bacteria, and individual differences in microflora may affect nitrate reduction (61, 86, 174).”
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    Interpretationreasoning
    § Abstract

    Treatments that increase nitric oxide bioavailability, reduce oxidative stress and inflammation, and perhaps improve mitochondrial health have the potential to improve arterial dysfunction in middle-aged and older adults.

    “it is reasonable to postulate that treatments that increase NO bioavailability, reduce oxidative stress and inflammation, and perhaps improve mitochondrial health, have the potential to improve arterial dysfunction in middle-aged and older adults.”
    Quote in the paperSubstantial claim

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    Interpretationreasoning
    § Abstract

    Inorganic nitrite, as well as dietary nitrate supplementation, represents a promising therapy for treatment of arterial aging and prevention of age-associated cardiovascular disease in humans.

    “In summary, inorganic nitrite, as well as dietary nitrate supplementation, represents a promising therapy for treatment of arterial aging and prevention of age-associated CVD in humans.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Findings from old mice and other preclinical models about sodium nitrite's effects on arterial stiffness and endothelial function are predictive of therapeutic effects in humans.

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    Premisecitation
    § Abstract

    In adults with inducible myocardial ischemia, venous infusion of sodium nitrite improves functional cardiac responses during dobutamine stress echocardiography, suggesting nitrite acts as a coronary vasodilator.

    “In adults with inducible myocardial ischemia, venous infusion of sodium nitrite improves functional cardiac responses during dobutamine stress echocardiography, suggesting that nitrite acts as a coronary vasodilator (76).”
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    Premisecitation
    § Abstract

    Inorganic nitrites and nitrates are milder vasodilators and have small or no effects on blood pressure in nonhypertensive adults.

    “inorganic nitrites and nitrates are milder vasodilators and have small or no effects on blood pressure in nonhypertensive adults (39, 63, 141).”
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    Premisenone given
    § Abstract

    Improvements in age-related vascular dysfunction with nitrite may be linked to increases in mitochondrial biogenesis and health.

    “and may be linked to increases in mitochondrial biogenesis and health.”
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    Premisecitation
    § Abstract

    Inhibition of nitric oxide using l-NAME markedly reduced endothelium-dependent dilation in young animals while having less effect in old mice, indicating that impaired endothelium-dependent dilation in old animals was mediated by reduced nitric oxide bioavailability.

    “Inhibition of NO using the NO synthase inhibitor l-NAME, markedly reduced EDD in young animals while having less effect in old mice, indicating that the impaired EDD in old animals was mediated by reduced NO bioavailability.”
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    Premisecitation
    § Abstract

    Nitrite treatment lessens renal injury in hypertensive rats and can protect against brain death-mediated renal injury while improving posttransplant renal function.

    “Nitrite treatment lessens renal injury in hypertensive rats (84) and can protect against brain death-mediated renal injury while also improving posttransplant renal function (89).”
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    Premisecitation
    § Abstract

    Sodium nitrite treatment normalized aortic nitrotyrosine staining in old mice, indicating amelioration of age-associated arterial oxidative stress.

    “Sodium nitrite treatment normalized aortic nitrotyrosine staining in old mice, indicating amelioration of age-associated arterial oxidative stress.”
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    Premisecitation
    § Abstract

    Nitrite did not affect endothelium-independent dilation to sodium nitroprusside, indicating that improvements in endothelium-dependent dilation were not induced by increased vascular smooth muscle sensitivity to nitric oxide.

    “Nitrite did not affect endothelium-independent dilation to sodium nitroprusside (171), indicating that the improvements in EDD were not induced by increased vascular smooth muscle sensitivity to NO.”
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    Premisecitation
    § Abstract

    Sodium nitrite reduced aortic pulse wave velocity in old mice, but did not influence aortic TGF-β, collagen, or elastin.

    “Sodium nitrite reduced aortic PWV in old mice, but did not influence aortic TGF-β, collagen, or elastin.”
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    Premisecitation
    § Abstract

    Nitrite, but not nitrate, therapy is effective in restoring blood flow and stimulating vascular remodeling, thereby preventing tissue necrosis in aged-diabetic mice after unilateral femoral ligation.

    “Nitrite, but not nitrate, therapy is effective in restoring blood flow and stimulating vascular remodeling, thereby preventing tissue necrosis in aged-diabetic mice after unilateral femoral ligation (12).”
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    Premiseown data
    § Abstract

    Sodium nitrite treatment reduced aortic pulse wave velocity in old mice to well below old controls and not significantly different from that in young animals.

    “Sodium nitrite treatment reduced aortic PWV in old mice to well below old controls and not significantly different from that in young animals.”
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    Premisecitation
    § Abstract

    Nitrite concentrations in plasma and large elastic arteries were lower in older animals, but sodium nitrite supplementation increased nitrite concentrations in old mice up to or above those of young control animals.

    “Nitrite concentrations in the plasma and large elastic arteries (aorta and carotid arteries) were lower in older animals, but sodium nitrite supplementation increased nitrite concentrations in the old mice up to or above those of young control animals (Fig. 2) (171).”
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    Premisecitation
    § Abstract

    In aortic rings from young mice studied ex vivo, administration of advanced glycation end products directly induced stiffening, an effect prevented by incubation with sodium nitrite.

    “In aortic rings from young mice studied ex vivo, administration of AGEs directly induced stiffening, an effect prevented by incubation with sodium nitrite (Fig. 3C).”
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    Premisecitation
    § Abstract

    Multiple preclinical studies suggest nitrite may be effective for prevention and/or treatment of many cardiovascular disorders or risk factors for cardiovascular disease including peripheral artery disease, atherosclerosis, chronic heart failure, stroke, diabetes, and hypertension.

    “multiple studies in preclinical models suggest that nitrite also may be effective for the prevention and/or treatment of many cardiovascular disorders or risk factors for CVD including peripheral artery disease (4, 69, 146), atherosclerosis (2, 3, 5, 127), chronic heart failure (32, 122), stroke (50, 82, 150), diabetes (138), and hypertension (22, 57, 58, 128).”
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    Interpretationown data
    § Abstract

    Short-term supplementation with sodium nitrite reduces aortic stiffness in old mice, perhaps by reversing advanced glycation end product formation.

    “these findings indicate that short-term supplementation with sodium nitrite reduces aortic stiffness in old mice, perhaps by reversing AGEs formation.”
    Quote in the paperSubstantial claim

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    Premisecitation
    § Abstract

    Aortic pulse wave velocity was higher in old mice and was associated with higher adventitial TGF-β and collagen levels, lower medial elastin, and higher adventitial and medial abundance of advanced glycation end products in the aorta.

    “Aortic PWV was higher in old mice and this was associated with higher adventitial TGF-β and collagen levels, and lower medial elastin and higher adventitial and medial abundance of AGEs in the aorta.”
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    Premisecitation
    § Abstract

    Sodium nitrite decreases plasma IL-6 concentrations and increases survival rate in a crush injury model in rats.

    “sodium nitrite decreases plasma IL-6 concentrations and increases survival rate in a crush injury model in rats (134)”
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    Interpretationreasoning
    § Abstract

    Sodium nitrite restores NO-mediated vascular endothelial function in part by reversing age effects on superoxide formation and BH4 oxidation, preserving eNOS-mediated NO production.

    “Sodium nitrite restores NO-mediated vascular endothelial function in part by reversing these effects of aging on superoxide formation and the oxidation of BH4, thus preserving eNOS-mediated NO production.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § Abstract

    Sodium nitrite treatment restores NO-mediated EDD in old mice by reducing superoxide production and oxidative stress.

    “Overall, these results are consistent with the idea that sodium nitrite treatment restores NO-mediated EDD in old mice by reducing superoxide production and oxidative stress.”
    Quote in the paperSubstantial claim

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    Premisecitation
    § Abstract

    Sodium nitrite treatment normalizes plasma C-reactive protein concentrations, leukocyte markers of inflammation, and improves vascular endothelial function in hypercholesterolemic mice.

    “a report showing that sodium nitrite treatment normalizes plasma C-reactive protein concentrations, leukocyte markers of inflammation, and improves vascular endothelial function in hypercholesterolemic mice (175)”
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    Interpretationcitation
    § Abstract

    Nitrite supplementation may induce mitochondrial biogenesis and improve mitochondrial health in arteries.

    “Nitrite supplementation also may induce mitochondrial biogenesis and improve mitochondrial health in arteries”
    Quote in the paperSubstantial claim

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    Interpretationreasoning
    § Abstract

    Nitrite therapy exerts a potent systemic and vascular anti-inflammatory effect that is associated with improvements in arterial function.

    “Taken together, these results support the view that nitrite therapy exerts a potent systemic and vascular anti-inflammatory effect that is associated with improvements in arterial function.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § Abstract

    Nitrite and nitrate are biologically important precursors of NO that have the potential to restore NO bioavailability in states of NO insufficiency via the nitrate-nitrite-NO pathway.

    “In conclusion, nitrite and nitrate are biologically important precursors of NO that have the potential to restore NO bioavailability in states of NO insufficiency via the nitrate-nitrite-NO pathway.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning
    § Abstract

    These observations have potentially important implications for the prevention and treatment of metabolic disorders, age-related physiological dysfunction, and chronic diseases.

    “Collectively, these observations have potentially important implications for the prevention and treatment of metabolic disorders, age-related physiological dysfunction, and chronic diseases.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given
    § Abstract

    Much of the work to date determining the beneficial effects of nitrite or nitrate supplementation per se has occurred using preclinical models or acute administration in humans.

    “However, much of the work to date determining the beneficial effects of nitrite or nitrate supplementation per se has occurred using preclinical models or acute administration in humans.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Abstract

    Mitochondrial dysregulation is implicated in impaired arterial function in human diabetes mellitus.

    “and human diabetes mellitus (166)”
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    Interpretationcitation
    § Abstract

    Nitrite therapy holds promise for treating hypercholesterolemia, hypertension, and chronic kidney disease.

    “Finally, nitrite therapy also holds promise for treating many other age-related clinical disorders associated with increased risk for CVD, including hypercholesterolemia (175), hypertension (58, 128), and chronic kidney disease (84).”
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38 of 38

  • The paper relies on this without support.

    Findings from old mice and other preclinical models about sodium nitrite's effects on arterial stiffness and endothelial function are predictive of therapeutic effects in humans.

    “In old mice, short-term oral sodium nitrite supplementation reduces aortic pulse wave velocity, the gold-standard measure of large elastic artery stiffness, and ameliorates endothelial dysfunction, as indicated by normalization of NO-mediated endothelium-dependent dilation.”
    “In summary, inorganic nitrite, as well as dietary nitrate supplementation, represents a promising therapy for treatment of arterial aging and prevention of age-associated CVD in humans.”

  • The paper relies on this without support.

    NADPH oxidase is the major oxidant-producing enzyme in vascular tissue.

    “the major oxidant-producing enzyme in vascular tissue, NADPH oxidase has been assessed (171)”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Sindler et al. demonstrated that dietary nitrite (50 mg/L in drinking water) was effective in the treatment of vascular aging in mice, evidenced by a reduction of aortic pulse wave velocity and normalization of NO-mediated endothelium-dependent dilation.

    “Sindler et al., recently demonstrated that dietary nitrite (50 mg/L in drinking water) was effective in the treatment of vascular aging in mice, which was evidenced by a reduction of aortic pulse wave velocity and normalization of NO-mediated endothelium-dependent dilation.”

    From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [91]

  • The improvements in vascular aging from dietary nitrite were mediated by reduction of oxidative stress and inflammation, linked to mitochondrial biogenesis and health.

    “They showed that these improvements were mediated by reduction of oxidative stress and inflammation, which were linked to mitochondrial biogenesis and health as a result of increased dietary nitrite.”

    From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [91]

  • Dietary nitrate/nitrite may be useful for the prevention and treatment of chronic age-associated hypertension.

    “These beneficial effects were also evident with dietary nitrate in their study [91], suggesting that dietary nitrate/nitrite may be useful for the prevention and treatment of chronic age-associated hypertension.”

    From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [91]

Cites

Flagged first, then by citations

Research works printed but not linked: 9

  1. Doganci S, 2012, Adv Clin Exp Med, 21, 713
  2. Ignarro LJ, 1986, J Pharmacol Exp Ther, 237, 893
  3. Johnson G, 1990, J Pharmacol Exp Ther, 252, 35
  4. Kortboyer J, 1998, National Institute for Public Health and the Environment
  5. Kortboyer JM, 1997, National Institute for Public Health and the Environment
  6. Lu XX, 2012, Sheng li xue bao [Acta physiologica Sinica], 64, 313
  7. Lüscher TF, 1997, Clin Cardiol, 20
  8. Torregrossa AC, 2011, J Geriatr Cardiol, 8, 230
  9. United States Department of Agriculture, 1999, Fed Reg, 64, 72168

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Authors
Sindler, A. L., DeVan, A. E., Fleenor, B. S., & Seals, D. R.
Affiliations
University of Colorado Boulder (US)
Corresponding author
Sindler, Amy L.
ORCID
Venue
Journal of Applied Physiology
Publisher
American Physiological Society
Published
2014-03-01
Volume
116
Issue
5
Pages
463-477
ISSN
  • 0161-7567 (ISSN-L)
  • 8750-7587
  • 1522-1601
DOI
10.1152/japplphysiol.01100.2013
PMC
PMC3949212
OpenAlex
W1971447711
Semantic Scholar
db1c89927730a09e0fec83af38a3600bdbfd01c7
Cited by
68
References
207
Citations by year
2025: 4 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 10 · 2015: 9 · 2014: 7
FWCI
1.61
Type
journal article
Language
en
Open access
Locations
  • Journal of Applied Physiology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (AG-000279, AG-013038)
  • National Heart, Lung, and Blood Institute (HL007822, R21HL107105, HL-107105)
  • National Center for Advancing Translational Sciences (TR000154)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords
inorganic nitrite, arterial aging, vascular aging, nitric oxide bioavailability, endothelial dysfunction, arterial stiffness, pulse wave velocity, oxidative stress, inflammation, mitochondrial biogenesis, dietary nitrate, cardiovascular disease prevention
MeSH terms
Aging, Animals, Arteries, Cardiotonic Agents, Cardiovascular Diseases, Endothelium, Vascular, Humans, Infusions, Intravenous, Nitrates, Nitric Oxide, Nitrites, Risk Factors, Sodium Nitrite, Dietary Supplements, Mice, Vascular Stiffness

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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