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The Longevity Intelligence Briefing The Neurogenesis IssueScience-backed levers for a brain that keeps growing Vol. 1 · Adult Brain Health · Spring 2025 Quick Takes
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High-fat, high-sugar diets and chronic alcohol use actively suppress hippocampal neurogenesis — through inflammation, insulin resistance, and oxidative stress. Zhao & Sabihi, 2026
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A single daytime nap has been shown to restore hippocampal function and improve declarative learning in human subjects — the evidence is direct and compelling. Ong et al., 2020
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Intensive cognitive training and enriched environments can measurably increase hippocampal volume in as little as 12 weeks in older adults with mild cognitive impairment. Fotuhi et al., 2016 Deep Dive You Can Sculpt Your Own Brain. Here Is the Evidence.More than a century ago, Santiago Ramón y Cajal wrote that any person could be "the sculptor of his own brain." The science of adult hippocampal neurogenesis is finally making that actionable. "Superagers" — people who remain cognitively sharp well into very old age — show higher rates of hippocampal neurogenesis than average. The question worth asking is not whether this matters, but what we can do about it. Four converging domains of evidence point toward a surprisingly coherent answer.
"Any man could, if he were so inclined, be the sculptor of his own brain." — Santiago Ramón y Cajal
Diet and metabolism. The evidence here is unusually blunt: what we eat shapes whether new neurons are born and survive. Diets high in fat and sugar, chronic overnutrition, and alcohol or opioid exposure suppress neurogenesis through inflammation, oxidative stress, and insulin resistance.[1] Caloric restriction and intermittent fasting paradigms, by contrast, increase neurogenesis and elevate BDNF — the brain's primary growth factor — in animal models, with emerging human data suggesting improvements in hippocampal-dependent cognitive tasks.[2] From animal models, diets rich in polyphenols (blueberries, curcumin, resveratrol), omega-3 fatty acids, and sulforaphane from cruciferous vegetables enhance neurogenesis via BDNF upregulation and antioxidant pathways.[2]
Evidence strength Polyphenols + omega-3s: strong animal data; emerging human evidence for caloric restriction
Practical lever Mediterranean-style eating, time-restricted feeding, minimising ultra-processed food
Sleep and circadian health. Sleep deprivation impairs the proliferation and survival of newborn neurons in animal models; fragmented or short sleep correlates with reduced hippocampal volume in humans.[1] The glymphatic system — the brain's waste-clearance network — is most active during deep sleep, and disruption here likely compounds neurogenic suppression. Particularly striking: a controlled study found that a single daytime nap restores hippocampal function and improves declarative learning in human participants.[3] This is one of the few areas where the human evidence is both direct and practically implementable today.
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Stress, mood, and neuroinflammation. Chronic psychological stress, glucocorticoid excess, and neuroinflammation all suppress adult hippocampal neurogenesis and promote dendritic atrophy — documented primarily in animal models.[4] The honest caveat: we have stress-reduction practices with strong evidence bases (mindfulness, therapy, exercise), but none has been formally tested for neurogenic effects in humans. The mechanistic logic is sound; the direct human trial remains to be done. Cognitive and social engagement. This is where the "use it or lose it" principle gets rigorous support. A 12-week personalised brain fitness programme in 127 older adults with mild cognitive impairment — combining cognitive training, neurofeedback, dietary coaching, fitness, and mindfulness — showed significant cognitive gains and, in the 17 participants who received MRI scans, 12 showed either reversal of hippocampal atrophy or increased hippocampal volume.[5] A separate 2022 memory-training study using episodic strategy training found relative hippocampal volume increases versus a no-training control, with effects persisting for weeks to months — though not clearly maintained at three years without continued practice.[6] Multimodal approaches combining brain stimulation, light therapy, music, gait training, and cognitive exercises have also shown enhanced neural activity in regions of interest in both young adults and older adults with MCI.[7]
Timeframe Measurable hippocampal changes documented within 12 weeks in multiple studies
Key implication Effects require continued practice — training is maintenance, not a one-time intervention
What makes this body of evidence unusual is its coherence. The same mechanisms — BDNF signalling, reduced inflammation, improved insulin sensitivity, glymphatic clearance — show up across all four domains. These are not independent levers. They appear to be parts of the same system. References
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Mycotoxins and the Gut: What the Research ShowsThe term "leaky gut" — or more precisely, intestinal permeability — refers to a breakdown in the tight junctions between intestinal epithelial cells. When those junctions loosen, partially digested food particles, bacterial fragments, and toxins can pass into the bloodstream and trigger systemic immune responses. It's an increasingly recognized contributor to chronic inflammation, a precursor to autoimmune conditions, and a factor in a range of health issues.
Several major mycotoxin families have now been studied for their effects on intestinal barrier function. The findings are consistent: these toxins don't just pass harmlessly through the gut. They cause problems. Aflatoxin (AFB1) Produced primarily by Aspergillus species on corn, peanuts, tree nuts, some spices, and oilseeds. Aflatoxin is best known as a potent liver carcinogen, but its gut effects are substantial. Aflatoxin is also immunotoxic, reducing secretory IgA (sIgA) — the front-line antibody of gut mucosal defense. This creates a compounding effect: barrier disruption plus impaired immune surveillance. Ochratoxin A (OTA) Produced by Aspergillus and Penicillium on cereals, coffee, dried fruits, wine, and some spices. OTA is primarily nephrotoxic, but recent reviews have shifted attention to its gut effects. A 2025 review explicitly frames the gut as both a target and modulator of OTA toxicity: OTA disrupts epithelial barrier integrity, increases intestinal permeability, and alters microbiota composition, with downstream metabolic and immune consequences (Więckowska et al., 2025). Sub-chronic low-dose OTA exposure in mice decreases overall microbial diversity, shifts the Firmicutes/Bacteroidetes ratio, and selectively inhibits some Firmicutes — suggesting a direct antimicrobial effect on beneficial taxa (Izco et al., 2021). Worth noting: most coffee sold in the US has acceptable levels of OTA. But some people may want products as close as possible to mold-free, which is why sourcing and testing matter (more on this below). Deoxynivalenol (DON) and Other Trichothecenes Produced by Fusarium on wheat, barley, oats, and other cereals. DON (also called vomitoxin) is acutely notorious for causing flu-like illness with vomiting, diarrhea, headache, and fatigue at high doses. At lower chronic doses, the gut effects are subtler but well-documented. DON directly injures intestinal epithelial cells, increases tight-junction permeability, disrupts microvilli, and activates TLR4/MyD88/NF-κB-mediated inflammation (Guerre, 2020). Research in animal models demonstrates that gut microbiota dysbiosis induced by DON can transmit toxicity to the liver and trigger systemic inflammation — suggesting the gut is not just a local target but a propagation site for broader harm (Jin et al., 2026). Zearalenone (ZEA) Another Fusarium toxin found in corn, wheat, barley, and other grains. ZEA is structurally similar to estrogen and is best known for its endocrine-disrupting effects — including effects on pubertal timing, menstrual irregularities, and fertility. Its gut effects are less publicized but real. Experimental ZEA exposure inhibits beneficial bacteria including Lactobacillus intestinalis and Clostridium leptum, driving an "unstable" flora associated with IBS (Wang et al., 2018). ZEA also induces mucosal immune activation, inflammatory cytokine production, and histologic damage to the small-intestinal mucosa, including villus injury and epithelial disruption. Fumonisins and Patulin Fumonisins (FB1, FB2), produced by Fusarium on corn and corn-based products, are associated with possible cardiovascular effects in animal models, though human data are less established. The practical takeaway: fresh corn is the safest type; the risk concentrates during drying and storage. Patulin, produced by Penicillium, Aspergillus, and Byssochlamys on apples and apple-based products, causes GI irritation and nausea at higher doses and shows genotoxic and immunotoxic effects in animal studies. It is a concern in juice and applesauce, but also because many of us cut out soft spots instead of discarding the whole apple. Which foods carry which possible mycotoxins:
Building Mold vs. Food Mold: Can You Tell the Difference? One of the most confusing areas for patients (and practitioners) is the interpretation of urine mycotoxin testing. A positive result does not automatically mean the person is living or working in a moldy building. It may simply reflect a diet rich in grains, nuts, spices, and dried fruit. Functional testing labs (such as MosaicDX MycoTOX) state explicitly that ingestion of contaminated foods and inhalation in moldy buildings are equally valid routes for the same analytes — and that the test cannot separate them. Mold-testing and remediation sources summarizing CDC and academic data note that positive urine findings in otherwise healthy people are expected from normal consumption of these foods, and correlate with high consumption of grains, for example. Suspect building-related mold exposure when you notice:
On internal colonization: this is possible but not well-proven. Conventional physicians normally diagnose colonization when they see a fungal ball in a body cavity such as the sinuses. A Category-by-Category Guide to Mycotoxin Risk in Food CoffeeCoffee is a frequent concern because green coffee beans can harbor ochratoxin A during post-harvest drying, especially in humid climates with poor processing controls. However, most coffee sold in the US tests below detection limits for OTA. If you already use an organic, small-batch, single-origin coffee from a company that tests its lots, there is no strong evidence to switch to a more heavily marketed "mold-free" brand. What matters is sourcing quality, storage conditions, and periodic verification. Brands that publish or make available third-party mycotoxin test results:
Tree Nuts Almonds and pistachios are under rigorous aflatoxin surveillance through the Almond Board, USDA, and export certification programs. Consignments exceeding regulatory limits are blocked from market. This does not mean risk is zero — it means the commercial supply chain has meaningful checks. Lot-to-lot variation still occurs. Practical guidance:
Spices A 2025 review of herbs, spices, and supplements concluded that chili/paprika, ginger, and various peppers are the most heavily contaminated spice group overall, frequently carrying aflatoxins plus OTA and sometimes fumonisins (Kanabus et al., 2025). Given this risk profile, choosing specialty brands with direct sourcing, small lots, and third-party microbial testing is a reasonable strategy. The supply chain matters: direct farm relationships and fast turnover reduce the window for mold to develop.
Grains Not all grains carry equal risk. Here is a practical comparison based on available survey data:
Dried Fruit There is no strong solution here from a mycotoxin standpoint. Raisins, currants, and sun-dried tomatoes are among the most consistently contaminated foods in survey data. Freeze-dried fruit may be a reasonable substitution if you want an alternative to fresh fruit: the process is faster and avoids the extended ambient-temperature drying that allows mold to proliferate. Once the package is opened, however, freeze-dried fruit last a short time. Seeds Sunflower seeds and sunflower oil warrant more caution than other seeds, with mycotoxin contamination documented in surveys. Preferred alternatives include pumpkin seeds, sesame seeds, and hemp seeds. Terrasoul explicitly states it independently tests every ingredient for mycotoxins, heavy metals, and microbials, with results available on request. The Safest Foods for GI Symptom Management If you are working through an active gut-healing protocol, or simply trying to reduce mycotoxin burden while addressing health issues, the following are reasonable foods to prioritize:
This isn't a permanent elimination diet. It's a diagnostic and therapeutic tool. A 4–8 week trial of these lower-risk staples, combined with a review of your pantry and living environment, can help clarify whether dietary mycotoxins are a meaningful contributor to your symptoms. Practical Guidance: What Actually Moves the Needle Buy smarter, not just "organic." USDA organic certification reduces pesticide risk but does not guarantee mycotoxin testing. What actually matters: brands that source in small lots with direct farm relationships, test each batch independently, and publish or share results on request. Organic is a reasonable starting filter; verified testing is the meaningful one.
IN CONCLUSION What I learned through this journey is that there are so many layers to improving health. I’ve been practicing functional medicine for 16 years. I was a conventional physician 21 years before that. Yet, there are more issues to discover when we stay curious! Why I use stool DNA tests with caution, if at all, in my practice
If you've ever sent a stool sample to one of those mail-in microbiome companies to learn about your gut health, here's something important you should know: the results depend heavily on which company you used — not just what's actually living in your gut. A new study put this to the test in a pretty clever way. What researchers didScientists at a top government lab (NIST) took stool from a single healthy person and carefully divided it into identical samples. They then sent the exact same material to seven different consumer microbiome testing companies — the kind that promise to tell you about your gut bacteria and what it means for your health. The idea was simple: if these tests are reliable, the same sample should produce roughly the same results everywhere. What they foundIt didn't. The companies came back with wildly different answers — different bacteria detected, different amounts reported, and different "health scores." In fact, the differences between companies were about as large as the differences you'd expect between two completely different people. A few companies at least got consistent results when testing the same sample multiple times. Others couldn't even agree with themselves. Perhaps most concerning: the same sample sometimes landed in different health risk categories depending on who analyzed it. "Normal" with one company could mean "at risk" with another — using the exact same stool. Why does this happen?Each company uses its own process from start to finish — how they handle the sample, how they extract DNA, how they sequence it, and especially how their software interprets the data. There are no universal standards, and the "healthy" vs. "unhealthy" cutoffs companies use are largely made up in-house, with little scientific backing. What this means for you
The bottom lineConsumer microbiome testing is a fascinating window into an emerging science — but the technology isn't ready to reliably guide health decisions. Researchers are calling for standardized testing practices, more transparency from companies, and proper regulation before these tests should be used clinically. This puts functional medicine physicians in a quandary because the article doesn't say which companies were at least consistent with themselves. If a company can reliably come up with the same answer, it might be believable that they can tell us when a person's stool is changing over time. Many clinicans may argue that "they know" because they have seen it in their practice. BUT don't get me started on the research showing how biased clinician's impressions typically are. For now, I absolutely would use these tests with enormous caution. |
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Blog AuthorDr. Myrto Ashe MD, MPH is a functional medicine family physician. Archives
April 2026
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