tangerine peels

Nobiletin Supplement For Sleep & Circadian Rhythm

[toc]When it comes to oranges, tangerines, and grapefruit, you may assume vitamin C is their top health benefit.

Perhaps it isn’t.

When you think about it, vitamin C is prevalent throughout the plant kingdom. This phytonutrient we’re about to talk about is not.

What is nobiletin?

Nobiletin is a type of flavonoid found in some citrus fruits. Research suggests it may have anti-inflammatory, anti-cancer, and anti-clotting benefits. These appear related to influencing the circadian cycle. Nobiletin influences hormones and metabolism while awake and asleep.

It has been studied for animal models of Alzheimer’s and Parkinson’s disease, with neuroprotective actions observed.

To date, there have been no human clinical trials evaluating it. However, you will find hundreds of peer-reviewed research articles and studies on it. (1)

Nobiletin food sources

The only natural food sources containing nobiletin are citrus fruits. It has been detected in seville oranges (Citrus aurantium), king oranges (Citrus nobilis), blood oranges (Citrus × sinensis), bitter oranges (Citrus × aurantium), tangerines (Citrus reticulate), and round kumquats (Fortunella japonica).

Many cultivars of citrus have it, particularly those with darker and more vibrant colors.

tachibana orange tree in China
In China, a Tachibana mandarin tree.

The highest natural food source of nobiletin will be the Tachibana, which is a variety of mandarin orange. When both the pulp and peel are included, it contains 54.3 mg per 100g.

Citrus peels (flavedo tissue) is the part with the highest concentration of nobiletin. The peel of the Dancy tangerine is the richest source, with 507 mg per 100g (3.4 oz).

Lemons do not contain any detectable nobiletin. Limes and grapefruit have a minuscule amount.

Regular orange juice has 0.07 to 0.20 mg of nobiletin per 100 mL (3.4 oz).

To get the dosage equivalent of a 50 mg nobiletin capsule, you would have to drink up to 19 gallons of fresh orange juice. (2) (3) (4)

How it may help circadian cycle

Given its antioxidant and anti-inflammatory properties, there’s no surprise that it’s being studied for a wide array of diseases. However, one of the most unique features being looked at is its ability to stabilize the body’s 24-hour cycle (circadian rhythm).

The benefits of proper circadian alignment extend far beyond just getting good sleep. The 2017 Nobel Prize in medicine was awarded to 3 scientists for this very topic. (5)

Their research proved:

  1. From fruit flies to mammals, at night a specific gene encodes a protein – it accumulates.
  2. During the day, this protein is degraded away.
  3. This cycle repeats every 24 hours.

In addition to your quality and quantity of sleep, this biological clock affects hormones, blood pressure, metabolism, and more:

circadian cycle events in humans during 24 hour period
Image credit: The Nobel Committee for Physiology or Medicine. Illustrator: Mattias Karlén.

When your circadian rhythm is off, research shows it can contribute to obesity, elevated blood sugar (and type 2 diabetes), heart disease, certain cancers, and some neurodegenerative diseases.

nobiletin circadian

In a study, the purple areas above indicate when the nobiletin dosage was given. You can see how in a dose-dependent manner, the wave (each wave being 1 day) flattens out. This effect is most pronounced with the highest dosage. (6)

While weight loss is not counted among the primary benefits, it is a known side effect of nobiletin usage in animal studies.

nobiletin weight loss

The chart above shows the body weight of mice fed a high fat diet. Those with nobiletin (red line) had a statistically significant lower body weight, when compared to the group fed the same high fat diet without it (black line).

When fed regular diets, lower body weight was also observed with nobiletin, but the difference was not as dramatic (blue vs. green lines). (7)

Although it’s not being investigate for diet pills, perhaps it should be?

Nobiletin supplement reviews

While natural food sources should not be ignored, it’s obvious that one would have to consume massive amounts of somewhat exotic citrus fruit peels, in order to get even a fraction of what a single capsule or pill contains.

Your stomach probably wouldn’t feel too great after eating a half-pound of Dancy tangerine peels, right?

Plus, how would you procure them? Places like Kroger and Whole Foods aren’t selling these rare cultivars.

Given that, for most people, nobiletin powder or powder-filled capsules make the most sense. Here are some good options:

Life Extension Circadian SleepLife Extension Circadian Sleep

They were the first to introduce nobiletin as a supplement. Each veggie capsule contains 50 mg of it, along with 1.5 mg of melatonin. Here’s the current price on Amazon.


Sytrinol is a patented formula made with polymethoxylated flavones (PMFs) from young citrus fruit and peels. In 3 clinical trials it was found to lower cholesterol and triglyceride levels.

While they don’t disclose the exact ratio, nobiletin and tangeretin are the two main flavones it contains.

Even though they don’t market it for such, using Sytrinol for insomnia also makes sense.

They sell this ingredient to various supplement manufacturers, so you can find a few which contain it.

For a more basic formulation, try Doctor’s Best Flavonoid Complex.

For a more advanced composition, check out NOW Sytrinol Cholesterol Formula.

Dosage instructions

As a dietary supplement to restore your circadian rhythm and help with sleep, Life Extension advises taking a 50 mg capsule of nobiletin once daily. They advise taking it before bedtime, however their supplement also contains melatonin.

If you’re taking a supplement without melatonin, taking it at dinner is probably a better time.

Nobiletin bioavailability may be best with a meal. This is because research has reported low water solubility and low oral bioavailability. (8)

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.