Some supplements act like stimulants and can keep your brain from shifting into sleep mode.Ingredients for energy or focus may linger too long and disrupt your natural sleep rhythms.Timing matters—taking certain supplements late in the day can make falling asleep much harder.

If you’ve cut back on caffeine, nailed your nightly bedtime routine and limited screen exposure close to bedtime, but you still can’t fall asleep, it might be time to take a look at your supplements. “People are often surprised to learn that supplements can be just as pharmacologically active as medications,” says Jessica Beal-Stahl, Pharm.D. Certain ingredients can interfere with sleep by stimulating the central nervous system, altering stress hormones or disrupting melatonin production—the hormone that signals to the body that it’s time to wind down. In this article, Beal-Stahl breaks down which supplements are most likely to keep you up at night, plus how timing and dose factor into the equation.

How Supplements Affect Your Sleep

For restful sleep to occur, your brain chemistry must shift from on-mode to off-mode. In other words, neurotransmitters that increase alertness and focus decrease, while melatonin increases to signal to your body that it’s time for sleep. Some supplements can disrupt this natural process.

“Many supplements that disrupt sleep work by increasing neurotransmitters tied to energy, focus or stress resilience,” says Beal-Stahl. While helpful earlier in the day, these effects can linger into the evening—especially when they have long half-lives (the amount of time it takes for half of a substance to be cleared from the body), are taken at higher doses or are stacked together.

Because supplements follow the same pharmacologic rules as medications, Beal-Stahl notes that timing and dosage matter just as much as the ingredient itself when it comes to sleep quality. Thanks to the circadian rhythm, “our bodies don’t respond to compounds identically at different times of day. We have variations in receptor sensitivity, enzyme activity and hormone responsiveness,” she adds.

Supplements Most Likely to Keep You Up at Night
Caffeine-Containing Supplements

Caffeine is one of the most common—and most overlooked—sleep disruptors, especially when it comes from supplements rather than coffee. In addition to obvious sources like energy drinks and pre-workout powders, caffeine can also be hidden in botanical ingredients such as guarana, yerba mate, green tea extract and kola nut, which are often added to products marketed for energy, focus or weight loss.

“Guarana is particularly frustrating because it’s not always recognized as a caffeine source,” says Beal-Stahl. Often listed simply as guarana extract, it can contain two to three times as much caffeine per gram as coffee beans, which may lead to higher overall caffeine intake than people realize—especially when products combine multiple stimulants.

Beyond how much caffeine you consume, the way your body processes caffeine also matters. Caffeine is mainly broken down by an enzyme called CYP1A2, and genetic differences can affect how quickly your body metabolizes it. “Some people metabolize caffeine slowly, meaning its effects last much longer,” Beal-Stahl says. For these individuals, even small amounts consumed in the afternoon may still be circulating at bedtime.

When stimulant-containing supplements are layered with caffeine from beverages throughout the day, their effects can accumulate, making it harder for the brain to transition into sleep mode at night.

Some Adaptogens (Rhodiola and Ginseng)

Adaptogens are often used to help manage stress and support energy, but when taken later in the day, they may interfere with sleep. Rhodiola is one commonly used adaptogen for stress and fatigue, as well as mental and physical performance. “It modulates neurotransmitters important for mental health and stamina, such as serotonin, norepinephrine and dopamine,” Beal-Stahl explains. While those effects may be helpful earlier in the day, taking rhodiola in the afternoon or evening can lead to restlessness—especially at higher doses or in people who are more sensitive to stimulants.

Ginseng can have similar effects. Beal-Stahl says ginseng modulates the body’s stress-response system and can increase alertness, with some forms more stimulating than others. Because its active compounds can remain in the body for several hours, she recommends limiting ginseng to morning use—or avoiding it altogether if sleep problems or anxiety are already a concern.

Brain-Health Supplements

Supplements marketed for focus or brain health may interfere with sleep, particularly when taken later in the day. L-tyrosine is one that supports the production of neurotransmitters involved in focus and concentration. “It’s a direct precursor to dopamine, norepinephrine, and epinephrine,” Beal-Stahl says, “and supplementation can significantly enhance catecholamine synthesis”—a process that prepares the body for action and triggers the ‘fight or flight’ response. This may be helpful for daytime focus, but it is counterproductive for sleep when taken after mid-afternoon.

DMA> (dimethylaminoethanol) may have similar effects. Often marketed for brain health or cognitive performance, DMA> influences acetylcholine, a neurotransmitter involved in arousal and REM sleep. Beal-Stahl notes that some people experience restlessness, difficulty falling asleep or unusually vivid dreams when using DMA>, particularly at higher doses or closer to bedtime.

Using brain boosters later in the day—or alongside other products intended to enhance energy or focus—can keep the nervous system in a more alert state into the evening. For people already struggling with sleep, Beal-Stahl recommends limiting these supplements to earlier hours or avoiding them altogether.

Vitamin D

Vitamin D is a commonly used supplement best known for supporting bone and immune health. Still, it also plays a role in processes tied to the body’s internal clock. , Research suggests vitamin D interacts with circadian pathways and melatonin, the hormone that helps regulate when you feel sleepy and when you feel alert.

“High-dose vitamin D, especially if taken at night, can interfere with melatonin production,” says Beal-Stahl. “Always take vitamin D in the morning,” she recommends. Taking vitamin D earlier in the day is generally less likely to interfere with sleep.

Other Tips for Better Sleep

If you have difficulty sleeping, a few simple habits can help you fall asleep faster and stay asleep longer, especially when combined with thoughtful supplement use:

Stick to a consistent sleep schedule. Going to bed and waking up at the same time each day helps reinforce your body’s internal clock.Protect your wind-down window. Dimming lights, limiting screens and avoiding mentally demanding tasks in the hour before bed can signal to the body and brain that it’s time to rest.Pay attention to afternoon inputs. Late-day caffeine, heavy meals or intense exercise can all affect how you sleep at night.Review supplements with fresh eyes. Take note of what you’re using and when—especially products meant to support energy, focus or performance.Get personalized guidance if needed. A pharmacist or healthcare provider can help you sort through medications and supplements to identify anything that may be interfering with sleep.

Our Expert Take

If you’re lying awake at night, your supplements may be worth a closer look. Ingredients that support focus and increase energy may interfere with the body’s stress response and circadian rhythm. This effect can be amplified when taken later in the day, at higher doses or alongside products with similar functions. If you’re unsure whether your supplements could be interfering with your sleep, talk to a healthcare provider for sleep-friendly adjustments.