Description: <b>MSM (Methylsulfonylmethane)</b> is a naturally occurring organosulfur compound often used as a dietary supplement for its anti-inflammatory and antioxidant effects. While most well-known for joint health.<br>
-MSM is actually a metabolite of DMSO (dimethyl sulfoxide)
<pre>
-Generally Recognized as Safe Possible Interactions: aspirin, warfarin, NSAIDS<br>
-Supplement dosage: 500mg 2-3times/day<br>
-Anti-inflammatory: ↓NF-κB, ↓COX-2 and iNOS
-↓STAT3
-↓Cyclin D1 and CDK4, halting cell cycle progression.
-↓MMP-2, MMP-9, VEGF limiting invasion.
</pre>
<br>
<b>Methylsulfonylmethane (MSM) — Cancer-Oriented Time-Scale Flagged Pathway Table</b>
<!-- Methylsulfonylmethane (MSM) — Cancer-Oriented Time-Scale Flagged Pathway Table -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer / Tumor Context</th>
<th>Normal Tissue Context</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>NF-κB inflammatory transcription</td>
<td>NF-κB ↓; COX-2/cytokines ↓ (reported)</td>
<td>Inflammation tone ↓</td>
<td>R, G</td>
<td>Anti-inflammatory signaling</td>
<td>One of the most consistent findings in MSM studies is suppression of NF-κB-linked inflammatory signaling.</td>
</tr>
<tr>
<td>2</td>
<td>STAT3 signaling</td>
<td>STAT3 phosphorylation ↓ (reported)</td>
<td>↔</td>
<td>R, G</td>
<td>Pro-survival pathway suppression</td>
<td>STAT3 inhibition has been reported in some breast and other tumor models; relevance depends on tumor type.</td>
</tr>
<tr>
<td>3</td>
<td>PI3K / AKT pathway</td>
<td>AKT signaling ↓ (reported; model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth modulation</td>
<td>Observed in certain cell lines; should be presented as context-dependent rather than universal.</td>
</tr>
<tr>
<td>4</td>
<td>ROS / redox modulation</td>
<td>ROS ↓ (often); oxidative stress tone ↓</td>
<td>Oxidative injury ↓</td>
<td>P, R, G</td>
<td>Redox buffering</td>
<td>MSM is generally described as anti-oxidative/anti-inflammatory rather than pro-oxidant; not a ROS-amplifying therapy.</td>
</tr>
<tr>
<td>5</td>
<td>Apoptosis induction</td>
<td>Caspases ↑; Bax ↑; Bcl-2 ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Cell death signaling</td>
<td>Apoptotic effects reported in vitro; usually downstream of inflammatory and survival pathway suppression.</td>
</tr>
<tr>
<td>6</td>
<td>Cell-cycle regulation</td>
<td>Cell-cycle arrest ↑ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Observed in some cancer cell systems; mechanism linked to signaling changes.</td>
</tr>
<tr>
<td>7</td>
<td>Migration / invasion (MMPs)</td>
<td>MMP expression ↓; migration ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Reduction in metastasis markers reported in certain preclinical models.</td>
</tr>
<tr>
<td>8</td>
<td>ER stress modulation</td>
<td>Stress signaling modulation (context-dependent)</td>
<td>Proteostasis support</td>
<td>R, G</td>
<td>Stress pathway modulation</td>
<td>Less consistent than NF-κB effects; should be kept qualified.</td>
</tr>
<tr>
<td>9</td>
<td>Chemo-/radiation interaction (theoretical)</td>
<td>May reduce inflammatory toxicity; may blunt ROS-based therapies</td>
<td>Normal tissue protection possible</td>
<td>G</td>
<td>Adjunct positioning</td>
<td>Because MSM is anti-oxidative/anti-inflammatory, positioning with strong pro-oxidant therapies should be considered carefully.</td>
</tr>
<tr>
<td>10</td>
<td>Translation constraint</td>
<td>Human anti-cancer efficacy not established</td>
<td>Generally well tolerated in common supplement ranges</td>
<td>—</td>
<td>Evidence limitation</td>
<td>Evidence base is largely preclinical; clinical oncology data are limited.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (early redox/inflammatory signaling shifts)</li>
<li><b>R</b>: 30 min–3 hr (NF-κB / STAT3 pathway modulation)</li>
<li><b>G</b>: >3 hr (cell-cycle, apoptosis, invasion phenotype changes)</li>
</ul>
<br><br>
For Alzheimer's (AD):<br>
Methylsulfonylmethane (MSM) in neurobiology is primarily framed as an anti-inflammatory and redox-buffering molecule, not a direct amyloid-clearing or tau-targeting drug. Evidence is largely preclinical (cell + animal models). Position it as a neuroinflammation and oxidative stress modulator.<br>
<pre>
-Anti-inflammatory: ↓TNF-α, IL-1β, IL-6
-↓ROS, ↑GSH, ↓NO
-may reduce Aβ plaque burden and tau hyperphosphorylation indirectly
-improves memory in rodents
</pre>
<br>
<b>Methylsulfonylmethane (MSM) — Alzheimer’s Disease (AD) Time-Scale Flagged Pathway Table</b>
<!-- Methylsulfonylmethane (MSM) — Alzheimer’s Disease (AD) Time-Scale Flagged Pathway Table -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>AD / Brain Context</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>Neuroinflammation (NF-κB / cytokine signaling)</td>
<td>Microglial activation ↓; IL-1β/TNF-α ↓ (reported)</td>
<td>R, G</td>
<td>Anti-inflammatory modulation</td>
<td>MSM’s most consistent neuro-relevant signal is suppression of NF-κB-driven inflammatory tone, which is implicated in AD progression.</td>
</tr>
<tr>
<td>2</td>
<td>Oxidative stress / redox buffering</td>
<td>Lipid peroxidation ↓; ROS tone ↓ (reported)</td>
<td>R, G</td>
<td>Neuroprotection (stress buffering)</td>
<td>MSM is generally described as antioxidant/anti-inflammatory rather than pro-oxidant; may help mitigate oxidative injury.</td>
</tr>
<tr>
<td>3</td>
<td>Mitochondrial function support</td>
<td>Mitochondrial stress ↓ (context-dependent)</td>
<td>R, G</td>
<td>Bioenergetic stabilization</td>
<td>Indirect support through reduced oxidative and inflammatory burden; not a primary mitochondrial activator.</td>
</tr>
<tr>
<td>4</td>
<td>ER stress / proteostasis modulation</td>
<td>UPR signaling ↓ (reported in stress models)</td>
<td>R, G</td>
<td>Proteostasis buffering</td>
<td>ER stress is relevant in AD pathology; MSM may attenuate stress signaling in some models.</td>
</tr>
<tr>
<td>5</td>
<td>Calcium homeostasis modulation</td>
<td>Excitotoxic stress ↓ (indirect)</td>
<td>P, R</td>
<td>Signal stabilization</td>
<td>Primarily indirect via inflammatory and oxidative stress reduction.</td>
</tr>
<tr>
<td>6</td>
<td>Aβ pathology (direct evidence)</td>
<td>Limited direct evidence of amyloid reduction</td>
<td>G</td>
<td>Indirect modulation</td>
<td>If effects occur, they are likely secondary to reduced oxidative stress and inflammation rather than direct amyloid targeting.</td>
</tr>
<tr>
<td>7</td>
<td>Tau phosphorylation</td>
<td>Limited direct mechanistic evidence</td>
<td>G</td>
<td>Indirect modulation</td>
<td>No strong mechanistic evidence that MSM directly modulates tau kinases; effects likely indirect.</td>
</tr>
<tr>
<td>8</td>
<td>Blood–brain barrier (BBB) considerations</td>
<td>CNS exposure plausible but not strongly quantified</td>
<td>R</td>
<td>PK consideration</td>
<td>Systemic exposure is good; CNS-specific pharmacokinetics are less clearly defined.</td>
</tr>
<tr>
<td>9</td>
<td>Cognitive outcome evidence</td>
<td>Limited direct human AD trial data</td>
<td>—</td>
<td>Translation constraint</td>
<td>Evidence base is largely mechanistic/preclinical; clinical AD efficacy not established.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (early redox/inflammatory signaling shifts)</li>
<li><b>R</b>: 30 min–3 hr (microglial signaling + oxidative stress modulation)</li>
<li><b>G</b>: >3 hr (phenotype-level neuroprotection effects)</li>
</ul>