Story at-a-glance

• Nobiletin, a molecule found in tangerines and oranges, was found to improve fat deposits, insulin resistance and high blood sugar in animals
• The mechanism of action has not been identified, but data show it does not interfere with a pathway used by metformin, a drug to treat diabetes
• Citrus fruits like oranges are high in vitamin C, which is known to support your immune system and protect against viral infections
• Healthy weight maintenance may be addressed using my KetoFast protocol combining simple, short fasting with eating delicious, healthy fats

Obesity is a condition defined by a marked accumulation of excess fat. Fat that grows just below the skin, called subcutaneous fat, is the kind that jiggles and wiggles. A second type can accumulate around your internal organs; this is called visceral fat.

Both can trigger health problems ranging from numerous types of chronic disease to potentially life-threatening conditions. The Centers for Disease Control and Prevention indicates your risk of 13 types of cancer increase when you are overweight or obese. These account for about 40% of all diagnosed cancers.1

Obesity contributes to the development of heart disease as it can lead to diabetes, increase your risk of high blood pressure, change the balance of your cholesterol levels2 and lead to metabolic syndrome.3 Other health risks include lower brain volume, bone and joint challenges, sleep apnea, liver problems and gallstones.4

According to the CDC, the prevalence of obesity rose from 30.5% in 2000 to 42.4% in 2018.5 Many use their body mass index (BMI) to determine if they are overweight or obese. This is a mathematical formula that uses height and weight to determine obesity.

In some cases, large muscle mass may skew the BMI and result in a false positive. In addition, your BMI doesn't help identify risks related to excess fat. A better method of determining your risk is calculating your waist-to-hip ratio since it indicates the presence of visceral fat, which your BMI will tell you nothing about.

Molecule in Oranges May Hold One Key to Addressing Obesity

One of the reasons low-fat diets became popular was because 1 gram of fat has more than twice the number of calories as 1 gram of carbohydrates — 9 versus 4.6 This led people to believe they could eat more carbohydrates and still maintain their weight or even lose weight. But years of data have revealed the opposite is true.

A diet heavy in carbohydrates increases your hunger and causes you to eat even more food. The rising number who struggle with being overweight and obese has prompted the study of phytonutrients found in plant foods.

Researchers from Western University in Canada7 studied nobiletin (NOB), a molecule found in tangerines and oranges. Their findings confirmed those from an earlier study which noted that “results suggest that NOB improves adiposity, dyslipidemia, hyperglycemia and insulin resistance.”8

The team found that feeding nobiletin to animals reduced the effects of a high-fat, high-cholesterol diet.9 Instead of growing heavier, the mice were leaner, had lower insulin resistance and had lower cholesterol when compared to a similar group fed just the high-fat, high-cholesterol diet.

This is the most recent published study from Murray Huff, Ph.D., who has been analyzing the effect of nobiletin on metabolism for more than 10 years. He commented on the results:10

“We went on to show that we can also intervene with nobiletin. We‘ve shown that in mice that already have all the negative symptoms of obesity, we can use nobiletin to reverse those symptoms, and even start to regress plaque build-up in the arteries, known as atherosclerosis.”

The researchers began with the hypothesis that nobiletin had an effect on AMPK, an enzyme that activates energy oxidation when levels of energy are low. Essentially, this would cause the body to burn stored energy.11 However, they found that even for mice that were fed a high-fat diet:12

" … nobiletin robustly prevented obesity, hepatic steatosis, dyslipidemia, and insulin resistance, and it improved energy expenditure in Ampkβ1 -/-, AccDKI, and iβ1β2AKO mice to the same extent as in WT controls. Thus, the beneficial metabolic effects of nobiletin in vivo are conferred independently of hepatic or adipocyte AMPK activation."

The author did not pinpoint how the molecule works, but Huff is encouraged since he believes it does demonstrate the molecule will not interfere with medications designed to interact with the AMPK system, such as metformin for the treatment of diabetes. He believes the next step is to begin human studies.

Evidence Suggests Nobiletin Has More Benefits

Nobiletin can been extracted from the tangerine peel used in traditional Chinese medicine.13 In one study, the extract, in combination with other flavonoids from the peel, was found to positively impact antioxidative defense in young chicks. Results from other studies have demonstrated significant health effects, including:14

Introduces anticancer properties in the lab, especially against colon cancer cells15

Protects against cardiac hypertrophy by inhibiting NADPH oxidase,16 an enzyme producing reactive oxygen species17

Relieves age-related cognitive impairment, as shown in a study involving mice18

Lessens cardiovascular disease in diabetes, based on results from an animal study19

Reduces myocardial injury following ischemia and reperfusion, as shown in an animal study20

Reduces seizures, as reported by researchers who conducted an animal study21

Improves arthritis, as shown in the lab and in animal studies22

Strengthens physical activity, including promoting healthy aging, exercise endurance and cold tolerance, also as demonstrated in an animal study23

Enhances autophagy and mitochondrial biogenesis24

Lowers blood pressure, according to results from an animal study25

Improves memory deficits and reduces neuronal loss, as shown in an animal study26

Vitamin C Supports Your Immune Function

Colds, flu and COVID-19 are viral, which means antibiotics are completely useless in treating them. Antibiotics are helpful if you have a secondary bacterial infection, but overuse is leading to antibiotic-resistant disease.

Citrus fruits, high in vitamin C, are important to your immune system. Other vitamin C-rich foods include green peppers, broccoli, Brussels sprouts, cauliflower and tomatoes.27 Researchers have focused on identifying pathways vitamin C may use in protection against influenza;28 it’s widely known to help children keep from getting upper respiratory tract infections.29

Organic orange peels are another option for vitamin C. One tablespoon of orange peel has 8.2 mg of vitamin C30 while 1 cup (16 tablespoons) of juice has 124 mg.31 When you multiply 8.2 mg by 16 tablespoons, the result is 131.2, just over the same amount in the juice. The peel has other health benefits you'll discover in "Eat Your Organic Orange Peels," but eating them comes with a caveat.

It is important to eat organic oranges, as much of the commercial crop from Florida has been liberally sprayed with antibiotics32 to help suppress greening disease. The disease is spread by the Asian citrus psyllid, which infects the trees with bacteria. Once infected, most trees will die within a few years. In the meantime they produce fruit that can't be sold.

As much as 90% of the citrus crops in Florida have been affected, which led the EPA to authorize the widespread use of antibiotics on the trees. Matt Wellington from US PIRG (Public Interest Research Groups) spoke to the Center for Infectious Disease Research and Policy (CIDRAP), saying:33

"The EPA is gambling with our life-saving antibiotics in its proposal to massively expand their use in citrus production. Spraying thousands of pounds of a medically important antibiotic on citrus trees violates the basic principle that these drugs should be used as little as possible, and only when necessary."

Following the first season of use, the University of Florida published a study demonstrating that using oxytetracycline for six months didn't have an effect on the viability of the trees. This also showed the initial data from the company providing the drugs that the EPA used for their decision, was flawed.34

The researchers did find that injecting the trees could decrease bacterial growth.35 However, it is expensive and not approved by the EPA. By choosing organic oranges you won't be exposed to the chance that an antibiotic has reached the fruit, or to what has remained on the peel. You also won’t be supporting a practice that will only increase the spread of antibiotic disease.

High Fructose Levels Lead to Insulin Resistance and Obesity

To achieve the results described in the Canadian study on nobiletin, researchers estimate you would have to drink 2.5 cups of orange juice a day.36 Unsweetened orange juice from frozen concentrate has 2.43 gm of fructose in each 100 gm (3.5 ounces)37 serving.38 In other words, if you were to drink 2.5 cups of orange juice each day, you would be consuming 13.88 gm of fructose in one sitting.

What this means in plain language is that while drinking orange juice may confer the benefits of nobiletin, it comes with added sugar that has a significant influence on obesity and related diseases. Another challenge is that your scale doesn't tell you how the fat you do have is distributed throughout your body.

Your waist circumference offers some idea, but even this measurement isn't foolproof. Some people appear thin but have the same health problems as people struggling with obesity, including high blood pressure, diabetes and heart disease. The underlying problems are visceral fat, insulin resistance and metabolic syndrome.

For the most part fructose is consumed in liquid form, often as high fructose corn syrup. However, even when the fructose is from fruit, the number of grams you eat still counts. The burden of metabolism will fall to your liver39 and excess fructose will promote the development of visceral fat collecting in your abdominal region. This raises your risk of heart disease and metabolic syndrome.

Although it's not inherently toxic, when you eat too much your liver can't handle the metabolism. As I've written before, I suggest keeping your total fructose below 25 gm per day, including whole fruit. The amount of fructose in 2.5 cups of orange juice is more than half this amount.

If you eat any other fruit, certain vegetables, processed foods or beverages,40 you are likely to easily go well over the limit and increase your risk of metabolic syndrome, even if you maintain your weight.

Simple Strategies Help Weight Management and Support Health

The challenges of weight loss and maintenance are affected by many factors, including what type of food you eat, when you eat, movement, sleep and exercise. The first two factors are foundational to your health and weight maintenance since, no matter how hard you try, you can't out-exercise a poor diet.

Your body needs the right nutrients to feed your cells, neutralize toxins and balance your weight. A great way to accomplish this is to use the KetoFast protocol I developed following the release of my best-selling book “Fat for Fuel.” Using the KetoFast protocol your body regains metabolic flexibility and increases your ability to burn fat for fuel.

This helps support your mitochondria and brain cells while reducing your risk for many chronic diseases associated with metabolic syndrome and obesity. The combination of fasting and eating a ketogenic meal plan is done in phases, so you aren't overwhelmed by the changes to how you eat. You'll discover more about the process at "KetoFast Explained."