One of the great breakthroughs in understanding the upsurge of obesity in recent years has been the discovery of the so-called “fat switch” (aka. metabolic master switch). It’s a metaphor for the idea that creating fat in our bodies can be turned on, or turned off. How marvelous it would be to flip the switch to off and start burning fat, instead of accumulating fat!

Well, we’ve arrived at that point, thanks to the pioneer work of experts like professor Richard J. Johnson, at the University of Colorado, Denver. Johnson has published several papers which are quite pivotal in our understanding of why we accumulate fat and why that has been driven to happen so much in the last 50 years or so.

Johnson wanted to understand the exact mechanism. Instead of walking the orthodox path, and using limited orthodox thinking (biochemistry, genetics, cellular pathology) he decided to tackle it from a much broader perspective: history, epidemiology, biology, anthropology, paleontology and evolutionary science.

He asked himself and his team why it was that some animals go through periods of rapid fat gain and then could somehow switch to a fat-burning mode. A hibernating bear, for example, could gain hundreds of pounds in the Fall and get fat for hibernation. But then it would switch to fat-burning mode and live off it’s fat deposits while sleeping for the whole winter. The fat gain mode exactly parallels the human “disease” we call metabolic syndrome (or diabesity), even including fatty liver deposits.

Whales do the same thing: humpback whales feed and feed in northern waters around Alaska. They get fat and then swim to Hawaii, there they don’t eat for half a year and lose all the excess weight.

Humpback whales don’t eat all summer (no problem!)

Even tiny little hummingbirds follow this same pattern. They feed on sugary nectar all day, get a fatty liver, but then through the night they are unmoving, don’t feed and by morning they are back to normal.

It’s so OBVIOUS you would wonder that doctors don’t know these simple truths and instead teach that fatty liver and diabetes are disease states that have to be “managed” and cannot be cured. Heck, bears, whales and hummingbirds manage themselves perfectly OK without any advice from doctors! No ill-health, no long-term obesity, no problem!

So maybe what we call “metabolic syndrome” is a natural process. It seems that nature uses it often. But since we can’t understand it or control it, then for doctors it is a danger, a disease. We don’t hibernate but maybe we are doing something that triggers the fat storage mode, just as if we were intending to hibernate?

Well, suffice it to say that Johnson’s entirely fresh way of looking at the problem has revealed some amazingly valuable answers. We now know there is a fat switch and how it works. Moreover, we know how to turn it off! Are you ready?

The AMP Pathway

The secret lies in a funny molecule called adenosine monophosphate (AMP) and its fate within the body. AMP is an energy molecule, obviously related to ATP (adenosine triphosphate) our main energy-bearing molecule.

In the process of metabolism of sugars (glucose) to create energy, AMP can be transformed by one of two enzymes, according to whichever “wins”. AMP deaminase (AMPD) leads to fat accumulation. AMP kinase (AMPK; sometime aka. 5' adenosine monophosphate-activated protein kinase) leads to fat burning.

In other words AMPK determines our body fat composition and especially the amount of visceral “belly” fat that we carry. Its activity is also tied to our life expectancy. When we are young, AMPK is more active, but as we age, the cellular AMPK activation decreases, leading to visceral fat accumulation and loss of muscle mass.

So there is the switch: AMPD we deposit unwanted fat; AMPK, we burn fat and get slim. Hooray for AMPK!

We get AMPD or AMPK—one or the other—according to influencing factors. Insulin resistance, for example, is associated with lack of AMPK and excess AMPD. We need insulin to metabolize excess glucose safely. If the body stops responding to insulin (insulin resistance), then the excess sugars in the diet convert automatically to unwanted fat.

That’s exactly what happens when we start to consume large quantities of sugar and carbs (most carbs convert readily to sugars). The healthy pathway is overloaded and breaks down. Instead of our mitochondria being able to process normal glucose quantities to ATP, they switch to fat depositing mode.

Leptin Resistance

But it gets worse: AMPD also leads to leptin resistance, one of the main initiators of over-eating! Leptin is a so-called “hunger hormone”, or appetite regulator, in that it switches off the feeling of wanting to eat. Its opposite number is another hunger hormone called ghrelin, which makes you feel peckish!

Readers will readily see that leptin is the one we want! It lessens our appetite. But if leptin resistance sets in, the body stops listening. In other words, eating will still trigger leptin release but it’s ignored. You go on eating anyway, eating a LOT!

Leptin resistance is crucial to overeating and gluttony.

All this is reversed by generating AMPK, which displaces AMPD. Where do we get AMPK? There are con-artists selling it on Amazon already, as if all you had to do was swallow a few capsules and disregard your lifestyle. Not true.

But there are important natural ways to ramp up AMPK. Changing how you eat is the most important, true: eat less or don’t eat at all for set periods… Intermittent fasting as it is called. Keto dieting, the latest craze, is effective too.

But there are herb substances too, which make the change for us. And one of the most outstanding of these is Berberine!

In fact it works so well, it is just as effective as metformin, the main diabetes medication used by doctors.

Uric Acid

There is another twist to the story, which gives us a surprising new biomarker, to tell how healthy our metabolism is; that’s uric acid. It is a marker for the AMPD pathway (therefore raised levels are bad).

We can guess there will be trouble anyway, because uric acid comes from the breakdown of DNA, RNA and ATP. These three crucial health molecules should not be being damaged in any significant way. But uric acid means something is wrong.

In fact animals in the wild seem to get very agitated and disturbed when uric acid appears in their blood. Prof. Johnson reasons that this is because matters have progressed beyond glycogen and fat consumption and the body is beginning to “consume” its own muscles, to provide energy.

Without knowing any physiology or biochemistry, the animal just knows to get busy and find food, quickly. In fact the emperor penguin—nature’s most impeccable father—will lose heart and abandon the egg he is nurturing and head for the sea, in order to find fresh food.

That’s how strong the uric acid signal is!

Uric acid should be on any blood test panel for someone overweight. It tells us which way the fat switch is set.

The good news? A number of studies have shown that Berberine significantly lowers blood uric acid (by causing it to be excreted in the urine).

Good For Diabetics

In a 2021 pilot study, Berberine significantly decreased HbA1c levels in diabetic patients. It was, in fact, comparable to the effect of metformin, a widely-used oral hypoglycemic pharmaceutical agent.

Since 1986 numerous published investigations have confirmed the anti-diabetic activity of Berberine and discovered various mechanisms, including the promotion of insulin secretion, the alleviation of insulin resistance, the inhibition of gluconeogenesis, the promotion of glucose uptake and glycolysis, the improvement of inflammation, the inhibition of several destructive enzymes, and the regulation of gut microbiota disorders.

Glycolysis means the breakdown of sugars and the ultimate depletion of fat deposits caused by excess blood sugar.²

It’s Not Just For Blood Sugar But Fats Too

We’ve been battered by the cholesterol hoax for decades. The level is not important; the balance of different lipids could be.

Berberine can be used as an alternative treatment for patients who do not tolerate statins, because of its lipid-lowering effects. The findings of a 2021 review (meta-analysis) demonstrated that Berberine alone can reduce dangerous triglycerides, total cholesterol, LDL and HDL cholesterol, fasting blood glucose and HOMA-IR levels in patients with metabolic disorders (HOMA-IR or Homeostatic Model Assessment for Insulin Resistance is the best measure we have of insulin resistance).

Compared with Berberine, metformin had little effect on lipid parameters. Compared with statins, Berberine is a miracle worker… and safer by far!

Berberine Promotes Insulin Secretion

Several in vitro studies have shown that Berberine can promote glucose-stimulated insulin secretion, which is clearly better than injecting it. It had a positive effect on pancreas size, islet cells (which secrete insulin) and pancreatic insulin secretion.³

Another study found that Berberine treatment for 8 weeks could significantly reduce fasting blood glucose (FBG), which is something we want to keep as low as possible. Years ago, FBG was widely proferred as the number one marker for how long you would likely live!

 

Insulin Resistance

In fact insulin resistance is one of THE markers for obesity, disordered metabolism and thus longevity. The mechanism is straightforward and not hard for the layman to understand. We eat too much sugar, insulin levels rise to lower blood glucose, typically by changing it to fat. But we eat MORE sugar and that means more insulin…

There comes a time when we consume so much sugar and other carbohydrates that insulin cannot get the blood glucose levels down. This is the state of pre-diabetes. If bad eating habits continue the blood glucose levels soar, so does insulin levels, but THE BODY IS NO LONGER LISTENING. Insulin cannot deal with the situation and this state we call insulin resistance.

It’s very bad news because insulin is very inflammatory in its own right. It tears up the lining of your blood vessels; that leads to heart disease, blood pressure  and stroke. VERY bad news.

You must get your insulin levels down, which means eat less (or no) sugar, and lower your hbA1C. BERBERINE DOES THIS FOR YOU. It’s ace at lowering glucose and insulin! Thus Berberine has emerged as a great herbal solution to pre-diabetes and diabetes.

In summary, Berberine is a potent oral hypoglycemic agent with modest beneficial effect on lipid metabolism. It is safe and the cost of treatment by Berberine is very low. It may serve as a new drug candidate in the treatment of type 2 diabetes.⁴

I could go on, there is more science yet. But this is surely enough for any savvy adult whose health is not perfect, and maybe has some weight issues, to decide to incorporate Berberine into a sound health protocol.

And did I point to its safety record, which is superb, and way safer than the new weight-loss drugs like Ozempic and Wegovy, which have no good safety trials? In fact good sources have stated categorically, that this class of drugs (GLP-1 agonists) should not be used, except for individuals with weight problems and OTHER medical issues.⁵