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You've been taking a supplement for weeks to manage stress, but you're not sure if it's working. Or maybe you've heard conflicting advice from wellness influencers, doctors, and supplement brands about what actually lowers cortisol. The supplement aisle is full of products claiming to support adrenal health and reduce stress hormones, but most lack clinical evidence, clear dosing guidelines, or honest discussions about side effects.
Superpower insight: Members who track their cortisol, DHEA-S, and inflammatory markers are better positioned to see whether a cortisol-lowering supplement is producing real physiological changes or just a placebo effect.
What Supplements Actually Do to Cortisol Levels
Cortisol is your body's primary stress hormone, released by the adrenal glands in response to physical or psychological stress. It's regulated by the hypothalamic-pituitary-adrenal (HPA) axis, a feedback loop that adjusts cortisol output based on what your body needs. When cortisol stays elevated for too long due to chronic stress, sleep deprivation, or metabolic dysfunction, it can drive weight gain, blood sugar dysregulation, immune suppression, and mood changes.
Supplements that lower cortisol work through different mechanisms. Some modulate the HPA axis directly, reducing the signal to produce cortisol. Others buffer the physiological stress response by supporting neurotransmitter balance or cellular energy production. A few work by blunting cortisol spikes triggered by acute stressors like exercise or mental tasks. The key distinction is whether a supplement lowers baseline cortisol, reduces stress-induced spikes, or both.
Ashwagandha (Withania somnifera)
Ashwagandha is an adaptogenic herb that modulates the HPA axis by reducing the overactivation of stress pathways. It contains bioactive compounds called withanolides, which appear to influence cortisol secretion at the level of the adrenal glands and the brain. Multiple randomized controlled trials and a 2024 meta-analysis confirm that ashwagandha supplementation significantly reduces serum cortisol compared to placebo. One RCT found a 27.9 percent reduction from baseline at 600 mg per day over 60 days. The most consistent effects are seen at doses of 300 to 600 mg per day of a standardized extract.
Phosphatidylserine
Phosphatidylserine is a phospholipid found in cell membranes, particularly concentrated in brain tissue. It appears to dampen cortisol release in response to acute stress by modulating the HPA axis at the pituitary level. Clinical trials show that 600 to 800 mg of phosphatidylserine per day can significantly blunt cortisol spikes after moderate exercise, with one study finding a 35 percent reduction in cortisol area under the curve. The effect is most pronounced during acute stress, not necessarily at baseline.
Rhodiola rosea
Rhodiola is another adaptogen with a long history in traditional medicine for stress resilience. It contains rosavins and salidroside, compounds thought to influence serotonin and dopamine pathways, which indirectly affect cortisol regulation. Clinical evidence is mixed. Some trials show modest reductions in stress-related symptoms and fatigue, but direct cortisol-lowering effects are less consistent than with ashwagandha. Effective doses range from 200 to 600 mg per day of a standardized extract.
How Cortisol-Lowering Supplements Affect the HPA Axis and Stress Response
The HPA axis is a tightly regulated feedback system. When your brain perceives stress, the hypothalamus releases corticotropin-releasing hormone (CRH), which signals the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH then tells the adrenal glands to produce cortisol. Once cortisol levels rise, they feed back to the hypothalamus and pituitary to shut down further release. This is called negative feedback.
Supplements like ashwagandha appear to enhance this negative feedback loop, making the system more sensitive to cortisol's signal to stop producing more. This prevents the chronic overactivation seen in prolonged stress. Phosphatidylserine works slightly differently by blunting the pituitary's release of ACTH in response to acute stressors, which means less cortisol gets produced in the first place during short-term stress events.
Effects on neurotransmitters and mood
Cortisol doesn't act in isolation. Chronic elevation disrupts neurotransmitter balance, particularly serotonin, dopamine, and GABA, which regulate mood, motivation, and anxiety. Preclinical studies show ashwagandha acts as a potent agonist at GABA receptors in the brain, which produces a calming effect and may partly explain why it reduces anxiety alongside cortisol in human trials. Rhodiola influences serotonin and dopamine pathways, which can improve mood and mental clarity even when cortisol changes are modest.
Effects on metabolic and immune function
Elevated cortisol promotes insulin resistance, increases blood sugar, and shifts the body toward fat storage, particularly around the abdomen. It also suppresses immune function by reducing the activity of white blood cells. Supplements that lower cortisol can improve insulin sensitivity and support immune resilience, but these effects are secondary to cortisol reduction. If your cortisol is already in a healthy range, further lowering it won't necessarily improve metabolism or immunity and may even impair the stress response you need for exercise recovery or acute illness.
What Clinical Research Actually Shows About Cortisol-Lowering Supplements
The evidence for cortisol-lowering supplements varies widely by compound, dose, and study design. Most research focuses on ashwagandha and phosphatidylserine because they have the most robust clinical data.
Ashwagandha
A 2024 systematic review and meta-analysis of randomized controlled trials found that ashwagandha supplementation significantly reduced cortisol levels, stress, and anxiety compared to placebo. The most consistent effects were seen with doses of 300 to 600 mg per day of a standardized extract (typically 5 percent withanolides) taken for 8 to 12 weeks. A separate crossover trial in aging overweight men found an 18 percent greater increase in DHEA-S compared to placebo, though that same study found no significant between-group differences in cortisol. Adverse effects in clinical trials were generally mild, including occasional digestive upset, though rare but serious cases of liver injury have been reported in post-marketing surveillance.
Phosphatidylserine
Clinical trials on phosphatidylserine show that it reduces cortisol response to acute stress, particularly exercise-induced cortisol spikes. A study in healthy men found that 600 mg per day reduced exercise-induced cortisol area under the curve by 35 percent compared to placebo. An earlier trial found that 800 mg per day for 10 days significantly blunted both ACTH and cortisol responses to exercise. Another trial showed improved mood and reduced perceived stress during mental tasks. The effect is most pronounced during acute stress, not at baseline, which means it's better suited for managing stress reactivity than chronically elevated cortisol.
Rhodiola rosea
Evidence for rhodiola is less consistent. A 2022 systematic review found that rhodiola improved symptoms of stress, fatigue, and burnout in several trials, but direct cortisol measurements were often not included or showed no significant change. One trial on burnout patients found improved attention and reduced fatigue, but cortisol levels were not significantly different from placebo. Rhodiola may work more through neurotransmitter modulation than direct HPA axis suppression.
Magnesium and L-theanine
Magnesium and L-theanine are often marketed for stress reduction, but their effects on cortisol are indirect. Magnesium supports the nervous system and may reduce stress-related symptoms, but clinical trials have not consistently shown direct cortisol-lowering effects. L-theanine, an amino acid from tea, promotes relaxation by increasing GABA and serotonin, but its impact on cortisol is minimal. These supplements may improve how you feel under stress without necessarily changing cortisol levels.
When and How to Take Cortisol-Lowering Supplements
Timing, dose, and form all affect how well a cortisol-lowering supplement works. Most clinical trials use specific doses and durations, and deviating from these can reduce effectiveness or increase the risk of side effects.
Ashwagandha
The most studied dose is 300 to 600 mg per day of a standardized extract (5 percent withanolides), typically split into two doses or taken once in the evening. Ashwagandha is fat-soluble, so taking it with a meal that contains fat improves absorption. Most trials show effects after 8 to 12 weeks of consistent use, though some people notice changes in stress and sleep within 2 to 4 weeks. Taking it in the evening may support better sleep by reducing nighttime cortisol, which should naturally be low.
Phosphatidylserine
Effective doses in clinical trials range from 600 to 800 mg per day, typically taken 30 to 60 minutes before a known stressor like exercise or a high-pressure work event. Because phosphatidylserine blunts acute cortisol spikes, it's most useful when timed around predictable stress. Taking it chronically at baseline may not provide the same benefit as strategic use before stress exposure. It's also fat-soluble, so absorption improves when taken with food.
Rhodiola rosea
Clinical trials use 200 to 600 mg per day of a standardized extract (3 percent rosavins, 1 percent salidroside), usually taken in the morning or early afternoon. Rhodiola has mild stimulant properties, so taking it late in the day may interfere with sleep in some people. Effects on fatigue and mental clarity may appear within 1 to 2 weeks, but stress-related benefits take longer.
Who Should Use Caution With Cortisol-Lowering Supplements
Not everyone responds the same way to cortisol-lowering supplements, and some people should avoid them entirely. Individual variation depends on baseline cortisol levels, the type of stress you're experiencing, existing health conditions, and medications.
People with low baseline cortisol
If your cortisol is already low due to adrenal insufficiency, chronic illness, or HPA axis dysregulation, further suppression can worsen fatigue, low blood pressure, and immune vulnerability. A 2026 case report described a 55-year-old woman who developed Cushingoid features and confirmed adrenal insufficiency after taking approximately 950 mg of ashwagandha daily for one year, with HPA axis suppression persisting six months after discontinuation. Testing baseline cortisol before starting a supplement helps avoid this.
Liver health
Multiple case reports and case series have documented ashwagandha-induced liver injury. Symptoms typically include jaundice, nausea, and abdominal discomfort appearing 2 to 12 weeks after starting supplementation. While rare, liver injury can be serious, particularly in people with pre-existing liver disease. If you develop signs of liver problems such as yellowing of the skin, dark urine, or persistent abdominal pain while taking ashwagandha, discontinue use and consult a physician.
Drug interactions
Ashwagandha may interact with thyroid medications, sedatives, and immunosuppressants. Clinical trials and case reports confirm it has thyroid-stimulating effects that can be problematic for people with hyperthyroidism or those taking thyroid hormone replacement, with documented cases of thyrotoxicosis in susceptible individuals. It also enhances the effects of sedatives and anxiolytics, increasing the risk of excessive drowsiness. Phosphatidylserine may interact with blood thinners and anticholinergic medications.
Pregnancy and breastfeeding
Safety data for ashwagandha, phosphatidylserine, and rhodiola during pregnancy and breastfeeding are limited. Ashwagandha has traditionally been avoided during pregnancy due to concerns about uterine stimulation. Until more research is available, these supplements should be used only under medical supervision during pregnancy or lactation.
Autoimmune conditions
Ashwagandha may stimulate immune activity, which could theoretically worsen autoimmune conditions like rheumatoid arthritis, lupus, or multiple sclerosis. Clinical evidence is limited, but caution is warranted if you have an autoimmune disorder.
Contaminated "adrenal support" supplements
Many over-the-counter "adrenal support" supplements contain glandular extracts from animal adrenal tissue. These products are not well regulated and have been found to contain undeclared thyroid hormones, corticosteroids, and other contaminants. A 2018 study in Mayo Clinic Proceedings analyzed 12 adrenal supplements and found that all contained detectable triiodothyronine (T3), with daily exposure up to 1,322 nanograms based on recommended doses, and most also contained steroid hormones, none of which were declared on the label. The FDA has issued warnings about infections and serious adverse effects from adrenal extract injections. If you're considering an adrenal supplement, choose products that have been third-party tested and avoid glandular extracts unless prescribed by a physician.
From Data to Action: Using Biomarkers to Guide Supplement Decisions
Knowing whether a cortisol-lowering supplement is working requires more than tracking how you feel. Cortisol levels fluctuate throughout the day, and subjective improvements in stress or sleep don't always correlate with measurable changes in cortisol. Testing relevant biomarkers before starting a supplement and tracking changes over time provides clearer insight.
Key biomarkers to consider include:
- Morning cortisol: Reflects baseline HPA axis activity and should be highest in the morning.
- DHEA-S: Balances cortisol's effects; low DHEA-S relative to cortisol suggests chronic stress.
- High-sensitivity C-reactive protein (hs-CRP): Elevated cortisol often drives inflammation; tracking hs-CRP shows whether cortisol reduction improves inflammatory status.
- Fasting glucose and insulin: Chronic cortisol elevation impairs glucose metabolism; improvements in these markers suggest metabolic benefit from cortisol reduction.
- Thyroid-stimulating hormone (TSH) and free T3: Ashwagandha can influence thyroid function; monitoring TSH and T3 ensures you're not over-stimulating the thyroid.
Directionality matters more than any single value. If your morning cortisol drops from 18 to 12 mcg/dL over 8 weeks of ashwagandha use and you feel better, that's meaningful. If it drops to 4 mcg/dL and you develop fatigue and low blood pressure, you've gone too far.
How Superpower Helps You Track What's Actually Working
If you're taking supplements to lower cortisol, Superpower's 100+ biomarker panel includes the markers that show whether your stress hormones are actually improving. You'll see your baseline cortisol, DHEA-S, inflammatory markers, and metabolic health indicators before you start, then track changes over time to know if your supplement strategy is working or if you need to adjust. You're not guessing based on how you feel. You're adjusting based on data that reflects what's happening inside your body.
What Supplements Actually Do to Cortisol Levels
Cortisol is your body's primary stress hormone, released by the adrenal glands in response to physical or psychological stress. It's regulated by the hypothalamic-pituitary-adrenal (HPA) axis, a feedback loop that adjusts cortisol output based on what your body needs. When cortisol stays elevated for too long due to chronic stress, sleep deprivation, or metabolic dysfunction, it can drive weight gain, blood sugar dysregulation, immune suppression, and mood changes.
Supplements that lower cortisol work through different mechanisms. Some modulate the HPA axis directly, reducing the signal to produce cortisol. Others buffer the physiological stress response by supporting neurotransmitter balance or cellular energy production. A few work by blunting cortisol spikes triggered by acute stressors like exercise or mental tasks. The key distinction is whether a supplement lowers baseline cortisol, reduces stress-induced spikes, or both.
Ashwagandha (Withania somnifera)
Ashwagandha is an adaptogenic herb that modulates the HPA axis by reducing the overactivation of stress pathways. It contains bioactive compounds called withanolides, which appear to influence cortisol secretion at the level of the adrenal glands and the brain. Multiple randomized controlled trials and a 2024 meta-analysis confirm that ashwagandha supplementation significantly reduces serum cortisol compared to placebo. One RCT found a 27.9 percent reduction from baseline at 600 mg per day over 60 days. The most consistent effects are seen at doses of 300 to 600 mg per day of a standardized extract.
Phosphatidylserine
Phosphatidylserine is a phospholipid found in cell membranes, particularly concentrated in brain tissue. It appears to dampen cortisol release in response to acute stress by modulating the HPA axis at the pituitary level. Clinical trials show that 600 to 800 mg of phosphatidylserine per day can significantly blunt cortisol spikes after moderate exercise, with one study finding a 35 percent reduction in cortisol area under the curve. The effect is most pronounced during acute stress, not necessarily at baseline.
Rhodiola rosea
Rhodiola is another adaptogen with a long history in traditional medicine for stress resilience. It contains rosavins and salidroside, compounds thought to influence serotonin and dopamine pathways, which indirectly affect cortisol regulation. Clinical evidence is mixed. Some trials show modest reductions in stress-related symptoms and fatigue, but direct cortisol-lowering effects are less consistent than with ashwagandha. Effective doses range from 200 to 600 mg per day of a standardized extract.
How Cortisol-Lowering Supplements Affect the HPA Axis and Stress Response
The HPA axis is a tightly regulated feedback system. When your brain perceives stress, the hypothalamus releases corticotropin-releasing hormone (CRH), which signals the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH then tells the adrenal glands to produce cortisol. Once cortisol levels rise, they feed back to the hypothalamus and pituitary to shut down further release. This is called negative feedback.
Supplements like ashwagandha appear to enhance this negative feedback loop, making the system more sensitive to cortisol's signal to stop producing more. This prevents the chronic overactivation seen in prolonged stress. Phosphatidylserine works slightly differently by blunting the pituitary's release of ACTH in response to acute stressors, which means less cortisol gets produced in the first place during short-term stress events.
Effects on neurotransmitters and mood
Cortisol doesn't act in isolation. Chronic elevation disrupts neurotransmitter balance, particularly serotonin, dopamine, and GABA, which regulate mood, motivation, and anxiety. Preclinical studies show ashwagandha acts as a potent agonist at GABA receptors in the brain, which produces a calming effect and may partly explain why it reduces anxiety alongside cortisol in human trials. Rhodiola influences serotonin and dopamine pathways, which can improve mood and mental clarity even when cortisol changes are modest.
Effects on metabolic and immune function
Elevated cortisol promotes insulin resistance, increases blood sugar, and shifts the body toward fat storage, particularly around the abdomen. It also suppresses immune function by reducing the activity of white blood cells. Supplements that lower cortisol can improve insulin sensitivity and support immune resilience, but these effects are secondary to cortisol reduction. If your cortisol is already in a healthy range, further lowering it won't necessarily improve metabolism or immunity and may even impair the stress response you need for exercise recovery or acute illness.
What Clinical Research Actually Shows About Cortisol-Lowering Supplements
The evidence for cortisol-lowering supplements varies widely by compound, dose, and study design. Most research focuses on ashwagandha and phosphatidylserine because they have the most robust clinical data.
Ashwagandha
A 2024 systematic review and meta-analysis of randomized controlled trials found that ashwagandha supplementation significantly reduced cortisol levels, stress, and anxiety compared to placebo. The most consistent effects were seen with doses of 300 to 600 mg per day of a standardized extract (typically 5 percent withanolides) taken for 8 to 12 weeks. A separate crossover trial in aging overweight men found an 18 percent greater increase in DHEA-S compared to placebo, though that same study found no significant between-group differences in cortisol. Adverse effects in clinical trials were generally mild, including occasional digestive upset, though rare but serious cases of liver injury have been reported in post-marketing surveillance.
Phosphatidylserine
Clinical trials on phosphatidylserine show that it reduces cortisol response to acute stress, particularly exercise-induced cortisol spikes. A study in healthy men found that 600 mg per day reduced exercise-induced cortisol area under the curve by 35 percent compared to placebo. An earlier trial found that 800 mg per day for 10 days significantly blunted both ACTH and cortisol responses to exercise. Another trial showed improved mood and reduced perceived stress during mental tasks. The effect is most pronounced during acute stress, not at baseline, which means it's better suited for managing stress reactivity than chronically elevated cortisol.
Rhodiola rosea
Evidence for rhodiola is less consistent. A 2022 systematic review found that rhodiola improved symptoms of stress, fatigue, and burnout in several trials, but direct cortisol measurements were often not included or showed no significant change. One trial on burnout patients found improved attention and reduced fatigue, but cortisol levels were not significantly different from placebo. Rhodiola may work more through neurotransmitter modulation than direct HPA axis suppression.
Magnesium and L-theanine
Magnesium and L-theanine are often marketed for stress reduction, but their effects on cortisol are indirect. Magnesium supports the nervous system and may reduce stress-related symptoms, but clinical trials have not consistently shown direct cortisol-lowering effects. L-theanine, an amino acid from tea, promotes relaxation by increasing GABA and serotonin, but its impact on cortisol is minimal. These supplements may improve how you feel under stress without necessarily changing cortisol levels.
When and How to Take Cortisol-Lowering Supplements
Timing, dose, and form all affect how well a cortisol-lowering supplement works. Most clinical trials use specific doses and durations, and deviating from these can reduce effectiveness or increase the risk of side effects.
Ashwagandha
The most studied dose is 300 to 600 mg per day of a standardized extract (5 percent withanolides), typically split into two doses or taken once in the evening. Ashwagandha is fat-soluble, so taking it with a meal that contains fat improves absorption. Most trials show effects after 8 to 12 weeks of consistent use, though some people notice changes in stress and sleep within 2 to 4 weeks. Taking it in the evening may support better sleep by reducing nighttime cortisol, which should naturally be low.
Phosphatidylserine
Effective doses in clinical trials range from 600 to 800 mg per day, typically taken 30 to 60 minutes before a known stressor like exercise or a high-pressure work event. Because phosphatidylserine blunts acute cortisol spikes, it's most useful when timed around predictable stress. Taking it chronically at baseline may not provide the same benefit as strategic use before stress exposure. It's also fat-soluble, so absorption improves when taken with food.
Rhodiola rosea
Clinical trials use 200 to 600 mg per day of a standardized extract (3 percent rosavins, 1 percent salidroside), usually taken in the morning or early afternoon. Rhodiola has mild stimulant properties, so taking it late in the day may interfere with sleep in some people. Effects on fatigue and mental clarity may appear within 1 to 2 weeks, but stress-related benefits take longer.
Who Should Use Caution With Cortisol-Lowering Supplements
Not everyone responds the same way to cortisol-lowering supplements, and some people should avoid them entirely. Individual variation depends on baseline cortisol levels, the type of stress you're experiencing, existing health conditions, and medications.
People with low baseline cortisol
If your cortisol is already low due to adrenal insufficiency, chronic illness, or HPA axis dysregulation, further suppression can worsen fatigue, low blood pressure, and immune vulnerability. A 2026 case report described a 55-year-old woman who developed Cushingoid features and confirmed adrenal insufficiency after taking approximately 950 mg of ashwagandha daily for one year, with HPA axis suppression persisting six months after discontinuation. Testing baseline cortisol before starting a supplement helps avoid this.
Liver health
Multiple case reports and case series have documented ashwagandha-induced liver injury. Symptoms typically include jaundice, nausea, and abdominal discomfort appearing 2 to 12 weeks after starting supplementation. While rare, liver injury can be serious, particularly in people with pre-existing liver disease. If you develop signs of liver problems such as yellowing of the skin, dark urine, or persistent abdominal pain while taking ashwagandha, discontinue use and consult a physician.
Drug interactions
Ashwagandha may interact with thyroid medications, sedatives, and immunosuppressants. Clinical trials and case reports confirm it has thyroid-stimulating effects that can be problematic for people with hyperthyroidism or those taking thyroid hormone replacement, with documented cases of thyrotoxicosis in susceptible individuals. It also enhances the effects of sedatives and anxiolytics, increasing the risk of excessive drowsiness. Phosphatidylserine may interact with blood thinners and anticholinergic medications.
Pregnancy and breastfeeding
Safety data for ashwagandha, phosphatidylserine, and rhodiola during pregnancy and breastfeeding are limited. Ashwagandha has traditionally been avoided during pregnancy due to concerns about uterine stimulation. Until more research is available, these supplements should be used only under medical supervision during pregnancy or lactation.
Autoimmune conditions
Ashwagandha may stimulate immune activity, which could theoretically worsen autoimmune conditions like rheumatoid arthritis, lupus, or multiple sclerosis. Clinical evidence is limited, but caution is warranted if you have an autoimmune disorder.
Contaminated "adrenal support" supplements
Many over-the-counter "adrenal support" supplements contain glandular extracts from animal adrenal tissue. These products are not well regulated and have been found to contain undeclared thyroid hormones, corticosteroids, and other contaminants. A 2018 study in Mayo Clinic Proceedings analyzed 12 adrenal supplements and found that all contained detectable triiodothyronine (T3), with daily exposure up to 1,322 nanograms based on recommended doses, and most also contained steroid hormones, none of which were declared on the label. The FDA has issued warnings about infections and serious adverse effects from adrenal extract injections. If you're considering an adrenal supplement, choose products that have been third-party tested and avoid glandular extracts unless prescribed by a physician.
From Data to Action: Using Biomarkers to Guide Supplement Decisions
Knowing whether a cortisol-lowering supplement is working requires more than tracking how you feel. Cortisol levels fluctuate throughout the day, and subjective improvements in stress or sleep don't always correlate with measurable changes in cortisol. Testing relevant biomarkers before starting a supplement and tracking changes over time provides clearer insight.
Key biomarkers to consider include:
- Morning cortisol: Reflects baseline HPA axis activity and should be highest in the morning.
- DHEA-S: Balances cortisol's effects; low DHEA-S relative to cortisol suggests chronic stress.
- High-sensitivity C-reactive protein (hs-CRP): Elevated cortisol often drives inflammation; tracking hs-CRP shows whether cortisol reduction improves inflammatory status.
- Fasting glucose and insulin: Chronic cortisol elevation impairs glucose metabolism; improvements in these markers suggest metabolic benefit from cortisol reduction.
- Thyroid-stimulating hormone (TSH) and free T3: Ashwagandha can influence thyroid function; monitoring TSH and T3 ensures you're not over-stimulating the thyroid.
Directionality matters more than any single value. If your morning cortisol drops from 18 to 12 mcg/dL over 8 weeks of ashwagandha use and you feel better, that's meaningful. If it drops to 4 mcg/dL and you develop fatigue and low blood pressure, you've gone too far.
How Superpower Helps You Track What's Actually Working
If you're taking supplements to lower cortisol, Superpower's 100+ biomarker panel includes the markers that show whether your stress hormones are actually improving. You'll see your baseline cortisol, DHEA-S, inflammatory markers, and metabolic health indicators before you start, then track changes over time to know if your supplement strategy is working or if you need to adjust. You're not guessing based on how you feel. You're adjusting based on data that reflects what's happening inside your body.
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