Kat Fu | Longevity Strategist | The Longevity Vault

Why Does NAD+ Drop Faster in Women After 40 — And What Does That Mean for Sleep?

During perimenopause and menopause, women lose NAD+ through two concurrent pathways: the age-related reduction that affects everyone, and an accelerated ovarian-specific depletion driven by rising CD38 and PARP activity in reproductive tissue. All three NAD+ synthesis pathways — kynurenine, Preiss-Handler, and salvage — show coordinated downregulation in aging oocytes (Di Emidio et al., 2024). No […]

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Why Does Perimenopause Give You Nightmares That Disrupt Your Sleep?

Sleep & 3AM Wakeups, Women's Hormones and Sleep / Kat Fu, M.S., M.S.

Perimenopause nightmares are a downstream consequence of REM sleep fragmentation. Estrogen decline reduces the brain’s ability to process emotional content during REM — the sleep stage where the amygdala is normally depotentiated (its reactivity lowered) through noradrenergic suppression. When REM is fragmented by hormonal hyperarousal, emotional material is not processed, and waking during a REM

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Why Are You Wired but Tired, and What Role Do Mitochondria Play?

Metabolic Sleep, Sleep & 3AM Wakeups / Kat Fu, M.S., M.S.

The wired-but-tired state is a measurable physiological condition. A meta-analysis of 20 studies found that people with chronic insomnia have elevated cortisol (SMD = 0.50), consistent with 24-hour hypothalamic-pituitary-adrenal axis hyperactivation (Dressle et al., 2022). Mitochondria sit at the center of this pattern: a PNAS study in mice demonstrated that mitochondrial function directly tunes adrenal

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Does the NLRP3 Inflammasome Disrupt Sleep?

Inflammatory Sleep, Sleep & 3AM Wakeups / Kat Fu, M.S., M.S.

Yes. The NLRP3 inflammasome is an intracellular immune complex that activates during sleep deprivation, releasing the inflammatory cytokines IL-1beta and IL-18 and triggering pyroptosis (inflammatory cell death) in neural tissue. NLRP3 knockout mice show reduced deep sleep rebound after sleep deprivation. In chronic insomnia with short sleep duration, peripheral NLRP3 components are upregulated compared to

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How Long Do Probiotics Take to Improve Sleep? What the Research Shows Week by Week

Autonomic Sleep, Sleep & 3AM Wakeups / Kat Fu, M.S., M.S.

Research shows initial sleep quality improvements at 4 weeks, with continued effects at 8 weeks and beyond. A 2024 meta-analysis of 15 trials comparing supplementation durations found that both 4-6 week and 8-16 week supplementation windows showed significant PSQI improvements (Ito et al., 2024). A Bifidobacterium breve trial documented measurable PSQI improvement at 4 weeks

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Is Your Insomnia a Nervous System Problem? How to Tell the Difference

Autonomic Sleep, Sleep & 3AM Wakeups / Kat Fu, M.S., M.S.

Insomnia can be driven by nervous system overactivation. The hyperarousal model — supported by EEG, neuroimaging, and neuroendocrine studies — shows that many people with chronic insomnia have measurable nervous system overactivation: elevated cortisol, higher heart rate at sleep onset, and reduced parasympathetic recovery. A 2023 review found that hyperarousal appears to be a persistent

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Can Your Eye Exam Predict How Long You’ll Live?

Circadian Sleep, Sleep & 3AM Wakeups / Kat Fu, M.S., M.S.

Deep learning models trained on retinal photographs can estimate how old the body is — independent of chronological age — with a mean error of under 3 years. When the predicted retinal age exceeds chronological age, each 1-year gap is associated with a 2% increase in all-cause mortality risk. The retinal age gap reflects vascular,

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How Does Your Vagus Nerve Actively Suppress Inflammation?

Autonomic Sleep, Sleep & 3AM Wakeups / Kat Fu, M.S., M.S.

The vagus nerve actively suppresses inflammation through a specific molecular circuit called the cholinergic anti-inflammatory reflex. Efferent vagal fibers release acetylcholine that binds to alpha-7 nicotinic acetylcholine receptors on macrophages, directly suppressing TNF-alpha production. A 2003 Nature study proved this receptor is strictly required: knockout mice lacking the alpha-7 subunit received no anti-inflammatory benefit from

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Does NAD+ IV Therapy Improve Sleep? What the Evidence Shows

Metabolic Sleep, Sleep & 3AM Wakeups / Kat Fu, M.S., M.S.

No controlled human trial has measured whether IV NAD+ infusions improve sleep. The Gindri 2024 review of 10 NAD-related RCTs evaluated fatigue, sleep, and anxiety endpoints but found evidence insufficient for firm recommendations; none of the trials used IV delivery with sleep as a primary outcome. A 2026 pilot comparing IV NAD+ to IV NR

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Is Your 3am Wakeup a Metabolic Emergency — Blood Sugar, Cortisol, and Mitochondrial Strain?

Metabolic Sleep, Sleep & 3AM Wakeups / Kat Fu, M.S., M.S.

The 2-4am window is when your metabolism is vulnerable. Blood glucose reaches its overnight nadir, cortisol peaks at approximately 3:40am biological time, and liver glycogen stores are at their lowest. When blood sugar drops below a critical threshold, counter-regulatory hormones fire — epinephrine, cortisol, glucagon — and these stress hormones trigger arousal. In metabolically healthy

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