Insomnia is maddening precisely because it defies logic. You need sleep. You want sleep. Your body is tired. Yet sleep won’t come — or won’t stay. And the harder you try, the worse it gets.

What many people don’t realize is that insomnia is often a symptom of something else going on in the body. While stress and poor sleep habits certainly play a role, persistent insomnia frequently has underlying physiological causes — thyroid dysfunction, blood sugar imbalances, hormonal shifts, nutrient deficiencies, or other conditions that disrupt the complex biology of sleep.

This matters because treating the symptom (insomnia) without addressing the cause rarely works long-term. Sleep medications may help temporarily, but if your thyroid is overactive or your blood sugar is crashing at night, the insomnia will persist until those underlying issues are addressed.

Blood testing can identify many of the medical conditions that cause or contribute to insomnia. Finding and treating the root cause often restores natural, restorative sleep — without relying on medications that don’t address the actual problem.

Understanding Insomnia

Insomnia isn’t just one thing. It manifests in different patterns, each of which can point toward different underlying causes. Understanding your specific pattern helps guide investigation.

Types of insomnia:

Sleep-onset insomnia: Difficulty falling asleep at bedtime. You lie awake for 30 minutes, an hour, sometimes longer before sleep finally comes. Your mind races, you can’t get comfortable, you watch the clock and calculate how little sleep you’ll get. This pattern is often associated with anxiety, an overactive mind, elevated cortisol, hyperthyroidism, stimulant effects (caffeine, medications), or circadian rhythm misalignment.

Sleep-maintenance insomnia: Waking up during the night and having difficulty returning to sleep. You might fall asleep fine but wake at 2 AM, 3 AM, or 4 AM and lie awake for hours. Sometimes you wake multiple times throughout the night. This pattern is often associated with blood sugar dysregulation (especially waking between 2-4 AM), hormonal changes (particularly in perimenopause), sleep apnea, pain conditions, alcohol use, or mood disorders. It’s one of the most frustrating types because you can fall asleep — you just can’t stay asleep.

Early morning awakening: Waking up too early (often 4-5 AM) and being unable to fall back asleep, even though you haven’t had enough rest. You lie there tired but alert, watching dawn arrive while wishing you could sleep another hour or two. This pattern is classically associated with depression, but can also relate to cortisol rhythm disruption (cortisol rising too early), age-related changes in sleep architecture, or an advanced sleep phase (internal clock shifted earlier).

Non-restorative sleep: Sleeping for what seems like adequate hours but waking unrefreshed, as if you hadn’t slept at all. You spend 7-8 hours in bed but wake feeling exhausted, not rested. This suggests sleep quality is poor even if sleep quantity seems adequate — often related to undiagnosed sleep apnea, periodic limb movements, chronic pain, or conditions that prevent deep, restorative sleep stages.

Mixed patterns: Many people experience combinations — difficulty falling asleep AND staying asleep, or different patterns on different nights. This complexity can make identification of the cause more challenging but also more important.

Acute versus chronic insomnia:

Acute insomnia lasts days to weeks and usually has an obvious trigger — stress from work or relationships, travel across time zones, illness, a major life event like a move or new baby, grief, or a change in schedule. It typically resolves when the trigger resolves or the body adapts. While unpleasant, acute insomnia is usually self-limiting.

Chronic insomnia persists for three months or longer, occurring at least three nights per week. This is when underlying causes become much more likely and investigation becomes important. Chronic insomnia rarely resolves on its own and often has physiological contributors that won’t go away without identification and treatment. Chronic insomnia also tends to become self-perpetuating — the anxiety about not sleeping makes it harder to sleep, creating a vicious cycle.

When insomnia warrants investigation:

• Persists for more than a few weeks despite good sleep habits
• Occurs without obvious external stressors or triggers
• Is accompanied by other symptoms (weight changes, mood changes, fatigue, night sweats, hot flashes, palpitations)
• Represents a significant change from your previous sleep patterns
• Doesn’t respond to standard sleep hygiene improvements
• Is severe enough to impair daytime functioning — affecting work, relationships, concentration, or mood
• Follows a specific, consistent pattern (always waking at the same time suggests a specific mechanism)
• Developed alongside other health changes
• Is present despite feeling extremely tired — you should be able to sleep but can’t

The impact of chronic insomnia:

Beyond the immediate misery of sleepless nights, chronic insomnia affects health in significant ways:

• Impaired cognitive function — memory, concentration, decision-making
• Increased risk of depression and anxiety
• Weakened immune function
• Increased inflammation
• Higher risk of cardiovascular disease
• Metabolic dysfunction and weight gain
• Increased pain sensitivity
• Reduced quality of life
• Accidents and errors due to fatigue

This is why treating insomnia matters — it’s not just about feeling rested, it’s about overall health.

The Biology of Sleep

To understand why medical conditions cause insomnia, it helps to understand what makes sleep happen in the first place.

The two-process model of sleep:

Sleep is regulated by two interacting systems:

Sleep pressure (Process S): The longer you’re awake, the more adenosine builds up in your brain, creating increasing pressure to sleep. This is why you feel sleepier the longer you’ve been awake. Caffeine blocks adenosine receptors, which is why it keeps you awake.

Circadian rhythm (Process C): Your internal 24-hour clock, controlled by the suprachiasmatic nucleus in the brain, creates a daily pattern of alertness and sleepiness. This clock is synchronized by light exposure and releases melatonin in the evening to promote sleep.

When these two systems are aligned and functioning properly, you feel alert during the day and sleepy at night. When they’re disrupted — by medical conditions, hormonal imbalances, or other factors — insomnia results.

What the body needs for sleep:

• Appropriate melatonin release: Melatonin signals the body that it’s time for sleep. Production should rise in the evening and fall in the morning.
• Declining cortisol: Cortisol, the alertness hormone, should be high in the morning and low at night. Elevated evening cortisol prevents sleep.
• Stable blood sugar: Blood sugar drops during the night can trigger adrenaline release, causing awakening.
• Balanced thyroid function: Both overactive and underactive thyroid can disrupt sleep.
• Appropriate body temperature: Core body temperature needs to drop for sleep onset. Conditions that affect temperature regulation affect sleep.
• Adequate neurotransmitter precursors: Serotonin, GABA, and other calming neurotransmitters require specific nutrients for production.
• Absence of pain and discomfort: Physical discomfort, including that from inflammation, keeps the nervous system activated.

Medical conditions can disrupt any of these requirements, leading to insomnia even when you’re doing everything “right” in terms of sleep hygiene.

Thyroid Dysfunction and Sleep

The thyroid gland affects virtually every system in the body, including sleep regulation. Both overactive thyroid (hyperthyroidism) and underactive thyroid (hypothyroidism) can cause sleep problems — though in different ways.

Hyperthyroidism and insomnia:

Hyperthyroidism — an overactive thyroid — is a classic cause of insomnia. Excess thyroid hormone puts the body in a state of metabolic overdrive:

• Increased nervous system activity — feeling “wired” or unable to calm down
• Elevated heart rate that persists at night
• Increased body temperature, causing night sweats and difficulty staying cool
• Anxiety and racing thoughts
• Shortened sleep duration despite exhaustion
• Difficulty both falling asleep and staying asleep

Other symptoms of hyperthyroidism include unexplained weight loss despite good appetite, rapid or irregular heartbeat, tremor, increased sweating, heat intolerance, frequent bowel movements, and anxiety or irritability.

Hypothyroidism and sleep:

Hypothyroidism — an underactive thyroid — more commonly causes excessive sleepiness and fatigue, but it can also cause insomnia through several mechanisms:

• Sleep apnea — hypothyroidism increases risk of obstructive sleep apnea due to tissue swelling and muscle weakness
• Restless legs syndrome — more common in hypothyroidism
• Muscle aches and discomfort that disrupt sleep
• Depression, which affects sleep architecture
• Cold intolerance making it difficult to get comfortable

The relationship between thyroid and sleep is bidirectional — poor sleep also affects thyroid function, potentially creating a cycle.

What to test:

TSH is the primary screening test. Low TSH suggests hyperthyroidism (the pituitary is reducing stimulation because thyroid hormone is already high). High TSH suggests hypothyroidism.

Free T4 and Free T3 measure actual thyroid hormone levels. In hyperthyroidism, these will be elevated. In hypothyroidism, they’ll be low.

TPO antibodies can identify autoimmune thyroid disease (Hashimoto’s or Graves’ disease), which can cause fluctuating thyroid levels and unpredictable sleep disruption.

Blood Sugar and Nighttime Awakening

One of the most common — and most overlooked — causes of sleep-maintenance insomnia is blood sugar dysregulation. If you consistently wake between 2-4 AM, blood sugar may be the culprit. This pattern is so characteristic that it should prompt blood sugar investigation in anyone experiencing it.

How blood sugar affects sleep:

During sleep, your body continues to need fuel — particularly your brain, which runs almost exclusively on glucose. Blood sugar naturally dips during the night as you’re not eating. In healthy individuals with stable blood sugar regulation, the body smoothly releases stored glucose (glycogenolysis) and produces new glucose (gluconeogenesis) to maintain stable levels through the night. You sleep undisturbed.

But when blood sugar regulation is impaired — due to insulin resistance, reactive hypoglycemia, or metabolic dysfunction:

1. Blood sugar may drop too low during the night (nocturnal hypoglycemia), especially 3-4 hours after falling asleep when the dinner meal has been fully processed
2. The body perceives this blood sugar drop as a crisis — an emergency requiring immediate action
3. The adrenal glands release stress hormones — adrenaline (epinephrine) and cortisol — to raise blood sugar back to safe levels
4. These stress hormones successfully raise blood sugar, but they also activate the fight-or-flight response
5. You wake up suddenly, often with anxiety, racing heart, sweating, or a feeling of alertness
6. You’re now wide awake, possibly anxious, heart pounding, and unable to return to sleep for hours

This pattern often occurs 3-4 hours after falling asleep, which typically means somewhere between 2-4 AM for people who fall asleep around 10 PM-midnight. The timing is remarkably consistent once this pattern establishes — you wake at nearly the same time each night.

Signs that blood sugar is affecting your sleep:

• Waking at a consistent time in the middle of the night (often 2-4 AM) without needing to urinate
• Waking suddenly with anxiety, racing heart, or sweating
• Waking feeling alert or “wired” rather than groggy
• Difficulty returning to sleep once awake — lying awake for hours
• Feeling hungry upon waking at night
• Sleep improves when you eat a small snack before bed (protein + fat works best)
• Worse sleep on nights when you ate a high-carb, low-protein dinner
• Better sleep when you avoid sugar and refined carbs in the evening
• Daytime symptoms of blood sugar issues — energy crashes, carb cravings, afternoon fatigue, feeling shaky or irritable when hungry
• Symptoms improved by eating more frequently during the day

The insulin resistance connection:

Insulin resistance makes blood sugar regulation inherently less stable. In insulin resistance, the body overproduces insulin to compensate for cellular resistance. This insulin overproduction can cause blood sugar to drop more dramatically than it should, especially during the overnight fast when there’s no food coming in.

The irony: people with insulin resistance often have high blood sugar averages but also experience significant blood sugar variability — including drops low enough to trigger stress hormone release at night. This is why people with metabolic dysfunction often have sleep problems even before they develop overt diabetes.

Reactive hypoglycemia:

Some people experience reactive hypoglycemia — blood sugar drops too low 2-4 hours after eating, especially after high-carbohydrate meals. If this occurs after dinner, the timing coincides perfectly with the typical 2-4 AM awakening window.

What to test:

Fasting glucose provides a snapshot of blood sugar regulation in the fasting state.

HbA1c reflects average blood sugar over 2-3 months, indicating overall glucose control and stability.

Fasting insulin is crucial and often overlooked — it can reveal insulin resistance even when glucose levels appear normal. Elevated fasting insulin indicates the body is struggling to maintain blood sugar stability, which can manifest as nighttime awakening. This is often the earliest detectable sign of blood sugar dysregulation.

The combination of these tests can reveal blood sugar dysregulation that might be causing your middle-of-the-night insomnia — even if you’ve never been told you have a “blood sugar problem.”

Cortisol and the Stress Response

Cortisol — your primary stress hormone — follows a natural daily rhythm that’s essential for healthy sleep. When this rhythm is disrupted by chronic stress, shift work, or other factors, insomnia often results. Understanding cortisol helps explain why stress makes sleep so difficult.

The normal cortisol pattern:

• Morning: Cortisol peaks within 30-45 minutes of waking (the cortisol awakening response, or CAR), providing the energy and alertness burst you need to start the day. This surge helps you get out of bed and feel alert.
• Daytime: Levels gradually decline through the afternoon as the initial morning surge dissipates
• Evening: Cortisol reaches its lowest point in late evening and early night, allowing melatonin to rise unopposed and sleep to occur. This is why you naturally feel sleepy in the evening.
• Night: Cortisol remains low during the first half of sleep, beginning to rise again in the early morning hours (around 3-4 AM) in preparation for awakening

This pattern evolved to match human activity — alertness and energy during the day when we need to be active, calm and sleepiness at night when we need to rest. When it’s working properly, you feel naturally energized in the morning and naturally sleepy at night.

How cortisol disruption causes insomnia:

Elevated evening cortisol: If cortisol remains high in the evening — due to chronic stress, late-night worry, evening exercise, caffeine, or other factors — it directly opposes sleep. Cortisol is an alerting hormone; it’s supposed to wake you up. If it’s elevated when you’re trying to sleep, sleep won’t come. You may feel “tired but wired” — exhausted yet unable to calm down enough to drift off. Your mind races, your body feels tense, and sleep feels impossible despite fatigue.

Flattened cortisol curve: Chronic, ongoing stress can lead to a pattern where the cortisol rhythm loses its normal variation. Cortisol doesn’t rise appropriately in the morning (causing morning fatigue and difficulty getting going) and doesn’t fall appropriately at night (causing evening wakefulness and insomnia). The curve becomes flat instead of having healthy peaks and valleys. This causes fatigue during the day when you want energy and alertness at night when you want sleep — exactly backwards from what you need.

Early morning cortisol spike: In some people, cortisol begins rising too early (3-4 AM instead of 6-7 AM), causing early morning awakening. You wake before dawn feeling alert, unable to sleep, even though you haven’t had enough rest. This is different from blood sugar-related awakening — it’s not accompanied by anxiety or racing heart, just unwanted alertness.

Trauma-related patterns: People with histories of trauma or chronic early-life stress may have permanently altered cortisol patterns that affect sleep. The stress response becomes dysregulated in ways that take significant effort to repair.

Sources of cortisol dysregulation:

• Chronic psychological stress — ongoing work pressure, relationship problems, financial worry, health concerns, caregiving burden
• Shift work or irregular schedules that conflict with natural circadian rhythms
• Chronic pain or illness — the body treats pain as a stressor
• Overtraining or excessive exercise, especially in the evening
• Blood sugar instability (low blood sugar triggers cortisol release as discussed above)
• Excessive caffeine, especially later in the day — caffeine stimulates cortisol release
• Sleep deprivation itself — poor sleep raises cortisol, which causes more poor sleep, creating a vicious cycle
• Evening screen use and artificial light exposure — can delay cortisol decline
• Underlying medical conditions affecting the adrenal or pituitary glands
• Anxiety disorders

What to test:

Morning cortisol (drawn between 7-9 AM, ideally within an hour of waking) reflects the cortisol awakening response. Very low morning cortisol may indicate adrenal insufficiency. Very high morning cortisol may indicate Cushing’s syndrome or significant chronic stress.

For a more complete picture of cortisol rhythm, salivary cortisol testing at multiple time points (waking, noon, evening, bedtime) can reveal patterns of dysregulation that a single morning blood test would miss. This four-point cortisol test shows whether the normal rhythm is intact or disrupted.

DHEA-S is sometimes tested alongside cortisol. DHEA is another adrenal hormone that can provide context for cortisol findings.

Iron Deficiency and Restless Sleep

Iron deficiency is strongly linked to sleep disorders, particularly restless legs syndrome (RLS) — an irresistible urge to move the legs that disrupts sleep.

How iron affects sleep:

Iron is essential for dopamine production in the brain. Dopamine helps regulate movement and also plays a role in sleep-wake cycles. When iron is low:

• Dopamine signaling is impaired
• Restless legs syndrome develops or worsens
• Periodic limb movements during sleep increase
• Sleep quality suffers even without obvious symptoms

Restless legs syndrome (RLS):

RLS causes uncomfortable sensations in the legs (crawling, tingling, aching, pulling) and an overwhelming urge to move them. Symptoms are worst in the evening and at night, particularly when lying still — making it difficult to fall asleep or stay asleep.

Signs of RLS:

• Uncomfortable sensations in legs when lying down or sitting
• Irresistible urge to move the legs
• Symptoms worsen in the evening and at night
• Symptoms improve with movement (walking, stretching)
• Difficulty falling asleep because you can’t keep your legs still
• Partner notices you kicking or moving legs during sleep

The iron connection:

Studies show that people with RLS often have low ferritin (iron stores), even when hemoglobin is normal. Iron supplementation frequently improves or resolves RLS symptoms, improving sleep.

What to test:

Ferritin is the key test. For RLS specifically, research suggests ferritin should ideally be above 75 for optimal symptom relief — higher than the lower limit of most standard reference ranges.

Serum iron, TIBC, and transferrin saturation provide additional information about iron status.

Hemoglobin should also be checked, though it can be normal even with iron deficiency severe enough to cause RLS.

Magnesium and Sleep Quality

Magnesium is involved in hundreds of enzymatic reactions in the body, including those that regulate sleep. Deficiency is common and often contributes to insomnia.

How magnesium affects sleep:

• GABA activation: Magnesium enhances GABA activity — the primary calming neurotransmitter that quiets the nervous system for sleep
• Melatonin regulation: Magnesium is involved in melatonin production
• Muscle relaxation: Magnesium helps muscles relax, reducing tension and restlessness
• Stress response modulation: Adequate magnesium helps regulate the stress response, reducing cortisol
• Blood sugar stability: Magnesium plays a role in insulin signaling and glucose metabolism

Signs of magnesium deficiency:

• Difficulty falling asleep or staying asleep
• Muscle cramps, twitches, or spasms
• Restless legs
• Anxiety or feeling on edge
• Headaches
• Fatigue
• Heart palpitations
• Constipation

Who is at risk for magnesium deficiency:

• Those with high stress levels (stress depletes magnesium)
• People who consume alcohol regularly
• Those taking certain medications (proton pump inhibitors, diuretics)
• People with GI conditions affecting absorption
• Those with diabetes or insulin resistance
• Older adults
• Those with diets low in magnesium-rich foods (leafy greens, nuts, seeds)

What to test:

Serum magnesium is the standard test, though it has limitations — serum levels are tightly regulated and may appear normal even when total body magnesium is depleted. A low serum magnesium definitely indicates deficiency, but a “normal” result doesn’t rule it out.

RBC magnesium (magnesium levels inside red blood cells) may be a better indicator of tissue magnesium status, though it’s not as widely available.

Vitamin D and Sleep

Vitamin D deficiency has been linked to sleep problems in multiple studies, including shorter sleep duration, poorer sleep quality, and increased daytime sleepiness.

How vitamin D affects sleep:

• Vitamin D receptors are found in brain regions that regulate sleep
• Vitamin D influences serotonin production, which is converted to melatonin
• Deficiency is associated with sleep apnea risk
• Low vitamin D is linked to inflammation, which can disrupt sleep
• Vitamin D affects pain perception — deficiency may worsen pain that disrupts sleep

What to test:

25-hydroxyvitamin D is the standard test for vitamin D status. Given the high prevalence of deficiency and its potential impact on sleep, this is worth checking in anyone with unexplained insomnia.

Sex Hormones and Sleep

Hormonal changes significantly affect sleep, which is why insomnia often emerges during perimenopause, menopause, andropause, or other times of hormonal transition. If your insomnia began or worsened during a hormonal shift, the connection is probably not coincidental.

Menopause and perimenopause:

Sleep problems are among the most common and distressing symptoms of the menopausal transition, affecting up to 60% of women. For many women, sleep disturbance is worse than hot flashes in terms of quality-of-life impact. Multiple interconnected factors contribute:

• Hot flashes and night sweats: Vasomotor symptoms are a major cause of nighttime awakening. A hot flash raises core body temperature and triggers sweating, which wakes you up. You may need to throw off covers, change clothes, or simply lie awake waiting for the sensation to pass. These episodes can occur multiple times per night, fragmenting sleep severely.
• Declining estrogen: Estrogen directly affects sleep architecture through multiple mechanisms. It helps regulate body temperature (hot flashes occur because temperature regulation is impaired). It influences neurotransmitters involved in sleep. It affects the circadian timing system. As estrogen declines, sleep becomes lighter and more fragmented even without obvious hot flashes.
• Declining progesterone: Progesterone has natural sedating and anxiolytic (anti-anxiety) effects — it acts on GABA receptors, the same receptors targeted by sleep medications like benzodiazepines. When progesterone declines, this natural calming effect is lost, making it harder to fall asleep and stay asleep.
• Increased sleep apnea risk: Estrogen and progesterone have protective effects on upper airway tone. Loss of these hormones increases sleep apnea prevalence significantly after menopause — in fact, postmenopausal women have similar sleep apnea rates to men of the same age.
• Mood changes: Anxiety and depression, more common during the perimenopausal transition due to hormonal fluctuations, significantly disrupt sleep. Mood symptoms may cause insomnia even when hot flashes are mild.
• Restless legs syndrome: RLS prevalence increases during menopause, possibly related to iron status changes or hormonal effects on dopamine signaling.

The perimenopausal period (the years leading up to menopause when hormones are fluctuating unpredictably) is often worse for sleep than established menopause, because the hormonal variability itself is destabilizing.

Low testosterone in men:

Low testosterone (hypogonadism) is associated with poor sleep quality and increased sleep apnea risk in men. The relationship is complex and bidirectional — low testosterone affects sleep, and poor sleep lowers testosterone.

How low testosterone affects sleep:

• Difficulty falling asleep
• Fragmented, non-restorative sleep
• Reduced time in deep sleep stages
• Increased risk of sleep apnea (testosterone affects upper airway physiology)
• Daytime fatigue and sleepiness despite seemingly adequate sleep hours
• Mood changes (depression, irritability) that affect sleep

Other symptoms of low testosterone include decreased libido, erectile dysfunction, reduced muscle mass and strength, increased body fat (especially abdominal), depressed mood, and difficulty concentrating.

The bidirectional relationship is important: sleep deprivation significantly reduces testosterone production. Men who chronically sleep less than 6 hours have markedly lower testosterone than those who sleep 7-8 hours. This creates a potential vicious cycle — low testosterone causes poor sleep, which further lowers testosterone.

Thyroid and sex hormone interactions:

Thyroid dysfunction can affect sex hormone levels, and vice versa. Hypothyroidism can lower testosterone in men and affect estrogen metabolism in women. Considering both thyroid and sex hormones together provides a more complete picture.

What to test:

For women with perimenopausal symptoms: FSH (follicle-stimulating hormone) and estradiol can help assess menopausal status. Elevated FSH with low estradiol indicates menopause or perimenopause. Progesterone may also be relevant, though levels vary significantly with the menstrual cycle if still cycling.

For men: Total testosterone and free testosterone, ideally drawn in the morning (between 7-10 AM) when testosterone levels naturally peak. SHBG affects how much testosterone is biologically available.

LH and FSH can help determine whether low testosterone is primary (testicular) or secondary (pituitary/hypothalamic) in origin.

Inflammation and Sleep

Chronic inflammation and sleep have a complex, bidirectional relationship. Inflammation disrupts sleep, and poor sleep increases inflammation — creating a self-perpetuating cycle.

How inflammation affects sleep:

• Inflammatory cytokines (IL-1, IL-6, TNF-alpha) affect sleep-regulating brain regions
• Inflammation increases pain sensitivity, causing sleep-disrupting discomfort
• Chronic inflammation affects neurotransmitter balance
• Inflammatory conditions often involve symptoms (pain, discomfort) that directly disrupt sleep

Sources of chronic inflammation:

• Autoimmune conditions
• Chronic infections
• Obesity — fat tissue produces inflammatory signals
• Poor diet — high in processed foods, sugar, and inflammatory fats
• Gut dysbiosis
• Chronic stress
• Sleep deprivation itself

What to test:

hs-CRP is a general marker of systemic inflammation. Elevated hs-CRP indicates inflammation from some source that may be contributing to sleep problems.

ESR is another inflammatory marker that can be elevated in various inflammatory conditions.

B Vitamins and Sleep

B vitamins play crucial roles in neurotransmitter synthesis and nervous system function. Deficiencies can affect sleep quality.

B12 and sleep:

Vitamin B12 is involved in melatonin production and circadian rhythm regulation. Deficiency has been associated with sleep disturbances, though the relationship is complex. Some people with B12 deficiency experience insomnia; others experience excessive sleepiness.

B6 and sleep:

Vitamin B6 is required for the conversion of tryptophan to serotonin, and serotonin to melatonin. It’s also needed for GABA synthesis. Deficiency can impair production of these sleep-promoting compounds.

Folate and sleep:

Folate (B9) works with B12 in numerous pathways. Deficiency is associated with depression and may indirectly affect sleep through mood effects.

What to test:

Vitamin B12 should be checked, especially in those at risk for deficiency (vegetarians, older adults, those with GI conditions).

Folate can be measured alongside B12.

B6 is less commonly tested but may be relevant if symptoms suggest deficiency.

Sleep Apnea: When Breathing Disrupts Sleep

Though not typically detected by standard blood tests, sleep apnea deserves mention because it’s extremely common, frequently undiagnosed, and causes insomnia patterns that may be mistaken for primary insomnia.

How sleep apnea causes insomnia:

• Repeated awakenings (often unremembered) fragment sleep
• May cause difficulty returning to sleep after awakening
• Can cause early morning awakening
• Leads to non-restorative sleep despite adequate hours in bed

Signs that suggest sleep apnea:

• Loud snoring
• Witnessed pauses in breathing during sleep
• Gasping or choking upon awakening
• Morning headaches
• Excessive daytime sleepiness despite adequate sleep time
• Waking with dry mouth
• Difficulty staying asleep
• Nocturia (waking frequently to urinate)

Risk factors:

• Obesity
• Large neck circumference
• Male sex (though women’s risk increases after menopause)
• Hypothyroidism
• Family history
• Alcohol use
• Certain facial structures

What to test:

Sleep apnea is diagnosed by sleep study (polysomnography), not blood tests. However, blood tests can identify conditions that increase sleep apnea risk:

• TSH — hypothyroidism increases sleep apnea risk
• Glucose and HbA1c — metabolic dysfunction is associated with sleep apnea
• Hemoglobin — may be elevated in chronic sleep apnea (compensation for low oxygen)

Medications and Substances That Affect Sleep

Before attributing insomnia to an underlying medical condition, consider whether medications or substances might be contributing.

Medications that can cause insomnia:

• Stimulants: ADHD medications, some antidepressants, decongestants
• Corticosteroids: Prednisone and similar medications
• Beta-blockers: Some blood pressure medications
• Thyroid medication: Especially if dose is too high
• Some antidepressants: SSRIs, SNRIs (variable effects)
• Diuretics: May cause nocturia
• Some asthma medications: Theophylline, albuterol

Substances that affect sleep:

• Caffeine: Half-life of 5-6 hours means afternoon coffee affects nighttime sleep
• Alcohol: May help you fall asleep but fragments sleep later in the night
• Nicotine: A stimulant that disrupts sleep
• Cannabis: Complex effects — may help some fall asleep but reduces REM sleep

The Testing Strategy for Insomnia

When insomnia is persistent and unexplained, comprehensive testing can identify underlying causes.

Core tests for unexplained insomnia:

Thyroid function:

• TSH
• Free T4
• Free T3

Blood sugar regulation:

• Fasting glucose
• HbA1c
• Fasting insulin

Iron status:

• Ferritin
• Iron

Vitamins and minerals:

• Vitamin D
• Vitamin B12
• Magnesium

Inflammation:

• hs-CRP

Hormones (based on symptoms):

• Morning cortisol
• For women: FSH, estradiol
• For men: Testosterone

Additional testing based on patterns:

• If middle-of-night awakening: prioritize glucose/insulin testing
• If restless legs: prioritize ferritin
• If difficulty falling asleep with anxiety: consider cortisol testing
• If perimenopausal symptoms: hormone panel
• If signs of sleep apnea: formal sleep study

What to Do With the Results

If thyroid dysfunction is found:

Hyperthyroidism requires treatment to lower thyroid hormone levels — once controlled, sleep typically improves dramatically. Hypothyroidism treatment with levothyroxine can also improve sleep, both directly and by reducing sleep apnea risk.

If blood sugar issues are found:

Addressing insulin resistance through dietary changes (reducing refined carbohydrates, increasing protein and healthy fats, especially at dinner), exercise, and potentially medication can stabilize nighttime blood sugar and eliminate middle-of-night awakening.

If iron deficiency is found:

Iron supplementation can improve restless legs syndrome and periodic limb movements, often significantly improving sleep quality. Improvement may take several weeks to months as iron stores are replenished.

If vitamin D deficiency is found:

Vitamin D supplementation may improve sleep quality, though results vary. Given the other health benefits of optimizing vitamin D, addressing deficiency is worthwhile regardless.

If magnesium deficiency is suspected:

Magnesium supplementation, particularly forms that cross the blood-brain barrier well (like magnesium glycinate or threonate), often improves sleep quality. Many people notice improvement within a few days to weeks.

If hormonal imbalances are found:

Treatment depends on the specific imbalance. Hormone replacement therapy may be appropriate for some menopausal women. Testosterone therapy may help men with confirmed low testosterone. These decisions require discussion with a healthcare provider.

If cortisol dysregulation is suspected:

Addressing the sources of chronic stress, improving sleep hygiene, and implementing stress reduction practices (meditation, exercise timing, limiting evening stimulation) can help restore normal cortisol rhythm.

When Tests Are Normal

If comprehensive testing returns normal results, the insomnia may be:

• Primary insomnia: A sleep disorder without an identified medical cause, often related to conditioned arousal. Over time, the bedroom and bedtime become associated with wakefulness and frustration rather than sleep. The anxiety about not sleeping becomes a self-fulfilling prophecy — you worry about whether you’ll sleep, which activates your stress response, which prevents sleep, which confirms your worry.
• Related to sleep hygiene: Inconsistent sleep schedule, screen use before bed (blue light suppresses melatonin), bedroom environment issues (too warm, too bright, too noisy), working or watching TV in bed, irregular routines
• Anxiety or depression-related: Mental health conditions significantly affect sleep. Anxiety often causes difficulty falling asleep (racing mind); depression often causes early morning awakening. These conditions may need direct treatment.
• Medication or substance-related: Carefully review all medications (prescription and over-the-counter), supplements, caffeine intake (including timing), alcohol use, and any other substances. Sometimes the culprit is something you wouldn’t have suspected.
• Sleep apnea: Which requires a sleep study to diagnose, not blood tests. If you snore, have witnessed breathing pauses, wake with headaches, or have excessive daytime sleepiness, a sleep study is warranted regardless of blood test results.
• Circadian rhythm disorder: Your internal clock may be misaligned with your desired sleep schedule. Delayed sleep phase (can’t sleep until very late, can’t wake up early) or advanced sleep phase (sleepy very early, awake too early) are examples. These often respond to light therapy and strategic timing adjustments.
• Environmental factors: Noise (including a partner’s snoring), light pollution, uncomfortable mattress, pets in bed, temperature issues
• Conditioned insomnia: After experiencing insomnia from any initial cause, the pattern can become self-perpetuating even after the original cause resolves. Your body has “learned” not to sleep in certain circumstances.

Normal blood tests are actually useful information — they rule out many medical causes, allowing focus on behavioral and psychological factors. Cognitive behavioral therapy for insomnia (CBT-I) is highly effective for primary and conditioned insomnia and is recommended as first-line treatment before sleep medications. CBT-I addresses the learned patterns that perpetuate insomnia and has lasting effects without the side effects or tolerance issues of medications.

The Bottom Line

Insomnia that persists despite good sleep habits often has an underlying physiological cause. Your body may be trying to tell you something — that your thyroid is overactive, that your blood sugar is unstable, that you’re deficient in iron or magnesium, that your hormones have shifted, or that inflammation is keeping your system activated.

Finding and addressing these underlying causes is far more effective than masking the symptom with sleep medications. Sleep medications don’t fix a thyroid problem — they just make you drowsy while your metabolism runs too fast. They don’t stabilize blood sugar — you still wake when your blood sugar crashes, you’re just more sedated. They don’t replenish iron stores — your legs still want to move. They may help you sleep tonight, but they don’t solve the problem, and they often lose effectiveness over time as tolerance develops.

The insomnia itself is the message. Something in your body isn’t working right, and inability to sleep is how it’s manifesting. Ignoring that message by overriding it with sedatives means missing the opportunity to address what’s actually wrong.

Blood testing can identify many of the medical conditions that disrupt sleep. A single round of comprehensive testing can screen for thyroid dysfunction, blood sugar problems, iron deficiency, vitamin deficiencies, hormonal imbalances, and inflammation — covering the most common physiological causes of chronic insomnia.

If you’ve been struggling with insomnia and haven’t found answers — if you’ve tried sleep hygiene and melatonin and chamomile tea and nothing works — comprehensive testing may reveal what’s actually going on. And addressing the root cause often does what no pill can: it restores natural, restorative sleep by fixing the underlying problem.

You deserve restorative sleep. Every night. If you’re not getting it, finding out why is the first step toward getting it back.

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Key Takeaways

• Insomnia is often a symptom of underlying conditions — thyroid dysfunction, blood sugar problems, hormonal imbalances, or nutrient deficiencies may be disrupting your sleep
• Different insomnia patterns suggest different causes — difficulty falling asleep, middle-of-night awakening, and early morning awakening have different underlying mechanisms
• Thyroid dysfunction directly affects sleep — hyperthyroidism causes a “wired” state that prevents sleep; hypothyroidism increases sleep apnea risk and causes restless legs
• Blood sugar instability causes middle-of-night awakening — if you wake consistently between 2-4 AM, blood sugar regulation may be the issue
• Cortisol should be low at night — chronic stress keeps cortisol elevated, preventing sleep even when you’re exhausted
• Iron deficiency causes restless legs syndrome — an often-overlooked cause of difficulty falling and staying asleep
• Magnesium deficiency is common and affects sleep — this mineral is essential for GABA function and muscle relaxation
• Hormonal transitions disrupt sleep — perimenopause, menopause, and low testosterone in men commonly cause insomnia
• Inflammation and sleep have a bidirectional relationship — each worsens the other
• Comprehensive testing can identify treatable causes — addressing the underlying condition often restores natural, restorative sleep