Best of The Weekly Thread: is berberine a magical molecule, the reality of aging and metabolism, and empathy provides clarity.

What is Berberine?

Berberine is a natural compound found in several plants, including the roots, stems, and bark of various species such as Berberis vulgaris (barberry), Coptis chinensis (goldthread), and Hydrastis canadensis (goldenseal). It has a long history of use in traditional Chinese and Ayurvedic medicine.

Berberine has gained attention for its potential health benefits. It has been studied for its antimicrobial, anti-inflammatory, and antioxidant properties. It may also help regulate blood sugar levels, support cardiovascular health, and aid in weight management. 

I will follow up in this segment with actual research to back up the above claims. Furthermore, our understanding of the incredible plethora of benefits of Berberine only seems to be growing as over 700 articles per year are published on this seemingly “magical” molecule. 

Berberine for Atherosclerosis 

A research paper released fairly recently in the prestigious journal Nature, titled Berberine treats atherosclerosis via a vitamin-like effect down-regulating Choline-TMA-TMAO production pathway in gut microbiota, shows a strong correlation between a reduction in plaque buildup in the carotid arteries and Berberine supplementation. This study came from a team of researchers who’ve been studying Berberine since 2004.

The study showed that Berberine supplementation reduced carotid artery plaque by 3.2% in 16 weeks. 

For only four months of Berberine supplementation as the one variable, this would be pretty remarkable, however, what makes this even more noteworthy is that in the same period of the study, another control group using traditional pharmaceuticals to treat their atherosclerosis actually showed a 1.9% increase in plaque buildup. 

I want to repeat this to really drive this point home...

In the 16 weeks of this study, subjects supplementing with Berberine twice daily saw a DECREASE in their plaque score by 3.2%, whereas those using a traditional pharmaceutical approach saw an INCREASE of 1.9%. 

Furthermore, the authors of the paper state: 

“The mode of action suggests a vitamin-like mechanism where Berberine acts on intestinal bacteria. Berberine caused TMAO reduction was seen in atherosclerotic patients in whom this therapeutic effect against plaque was observed. Thus, it is justified to develop Berberine as a medicine for the treatment of atherosclerosis.”

What you need to know about TMAO is that there is a correlation between high levels of TMAO produced in the gut and an increase in arterial plaque buildup. It appears that Berberine improves the gut ecology in a way that improves overall gut health, which has the effect of reducing TMAO. 

Now, let’s reiterate a pretty profound statement made by the researchers and authors of this paper: 

“…thus, it is justified to develop Berberine as a medicine for the treatment of atherosclerosis.”

In a time where it seems we must put a disclaimer on everything, and when it comes to any nutritional or dietary supplement, the disclaimer, “is not used to treat or cure…” must always be used, it’s pretty extraordinary for these researchers to make the statement that Berberine should be used as “a medicine for the treatment of atherosclerosis.”

Berberine for Preventing Metabolic Syndrome

There is ample amounts of research showing Berberine can be useful in preventing metabolic syndrome and Type II Diabetes by activating a protein complex called AMPK

AMPK is also activated during exercise and periods of fasting (including intermittent fasting), meaning this molecule can work similarly in some ways on the body as exercise and fasting, and will compound the benefits yielded from said positive lifestyle habits. This is also why Berberine can be referred to as an “exercise mimicker” or “fasting mimicker”. (For this purpose, I would never recommend Berberine in lieu of exercise, but rather, in conjunction to compound its benefits).

Berberine has been found to activate the protein complex known as AMP-activated protein kinase (AMPK),. AMPK is a key regulator of cellular energy metabolism.

Here’s a quick breakdown of how Berberine activates AMPK and its potential role in preventing metabolic syndrome:

1. Increased AMP. Berberine helps raise the levels of adenosine monophosphate (AMP) in cells. When cellular energy levels are low, the concentration of AMP increases.

2. AMPK activation. Higher levels of AMP stimulate the activation of the AMPK protein complex. Berberine enhances this activation process.

3. Metabolic effects. Once activated, AMPK initiates a variety of metabolic effects. It enhances glucose uptake in cells, leading to improved insulin sensitivity and better blood sugar control. It also promotes fatty acid oxidation, helping to burn stored fat. Additionally, AMPK activation can inhibit the production of glucose in the liver and reduce inflammation.

Through the activation of AMPK, Berberine influences multiple metabolic pathways, potentially contributing to the prevention or management of metabolic syndrome.

To read more on metabolic syndrome and its impact on longevity, CLICK HERE.

Berberine for Weight Loss 

Berberine has been shown to induce a secretion of GLP-1. The popular weight loss molecule Semaglutide, also known as Ozempic, is also in the category of a GLP-1.

What is a GLP-1? 

GLP-1 stands for Glucagon-Like Peptide 1. It is a hormone produced in the gut that plays a crucial role in regulating blood sugar levels. GLP-1 helps stimulate the release of insulin, which lowers blood sugar, and also reduces the production of glucagon, a hormone that raises blood sugar. Additionally, GLP-1 slows down the rate at which food moves through the stomach, leading to increased feelings of fullness and reduced appetite. Due to these effects, GLP-1-based medications are used in the treatment of type 2 diabetes and obesity.

Due to Berberine’s effects on gut ecology, its ability to stabilize and help metabolize blood sugar, and its ability to induce secretion of GLP-1, Berberine could be a valuable aid and supplement to any well-rounded weight loss/management program. 

This consideration could be further bolstered when you take into account the potentially significant benefits it could also provide to cardiovascular health, and its ability to also boost the anti-aging protein complex AMPK. 

I use a form of Berberine calledHydroxyberberine” from Alpha Lion that is a more bioavailable form of Berberine. I take one capsule, twice daily.

Why does our metabolism slow as we age?

A paper I recently came across titled, “Metabolic changes in aging humans: current evidence and therapeutic strategies” aimed to best answer that question based on a review of data showing changes in fat gain (adiposity), muscle, and hormones related to aging. 

Here’s what they found. 

As fat cells get older, they begin to misbehave, and this dysfunction does cause them to hold on to fat more tightly. 

Furthermore, a newer discovery was made. The authors state in the paper:

Immune cell infiltration increases with age, and accumulation of age-dependent regulatory cells is seen. This is a newly characterized aspect of fat cell biology.” 

This new discovery shows that as you age, this accumulation of immune cells in your fat cells causes the fat cells to misbehave, and this is a new factor for consideration (and further research) as to why your fat cells become more stubborn with age. 

As you age, you also have an accumulation of senescent fat cells, if they don’t go through apoptosis and die, they recruit other functional fat cells to then also act like senescent cells, causing further fat cell dysfunction. 

What are senescent cells? 

Senescent cells are cells that have entered a state of irreversible growth arrest, meaning they no longer divide and proliferate. They are characterized by changes in gene expression and the secretion of various molecules, collectively known as the senescence-associated secretory phenotype (SASP). 

Senescent cells can accumulate in tissues over time and are associated with aging and age-related diseases. While senescence serves as a protective mechanism to prevent damaged cells from becoming cancerous, the accumulation of senescent cells can have detrimental effects on tissue function and contribute to age-related decline. 

Senescent cells are often referred to as “zombie cells”, and are oftentimes at the heart of our autoimmunity, cancer, and now we’re realizing, fat or weight gain. 

How do we stop “zombie (senescent) cells” from accumulating?

Through a process known as apoptosis. 

Apoptosis, also known as programmed cell death, is a natural process that eliminates unwanted or damaged cells in a controlled manner. It plays a crucial role in maintaining tissue homeostasis and removing cells that are no longer needed or that pose a risk to the organism. 

In relation to senescent cells, apoptosis serves as a mechanism to eliminate these cells from tissues. Ideally, senescent cells should undergo apoptosis and be cleared from the body. However, in some cases, senescent cells evade apoptosis and persist in tissues, leading to their accumulation. This impaired clearance of senescent cells can contribute to the detrimental effects associated with aging and age-related diseases.

What induces apoptosis?

Certain longevity-boosting lifestyle habits such as exercise and fasting induce apoptosis. There are also certain research backed herbs known as “Senolytics” that will induce apoptosis just through consumption.

I know recommending exercise and fasting (both intermittent and periodic extended fasting) probably isn’t super noteworthy, however, what this research shows us is that there’s far more benefit to exercise and fasting from a fat loss perspective. This also shows us that there’s a far greater picture to paint with respect to fat loss being more than just calories in and calories out. 

Gaining greater understanding of all the mechanisms at play that benefit us from positive lifestyle habits like fasting and exercise, will help you better understand what’s going on inside the body, and maybe leave you placing an even greater emphasis on implementing said lifestyle habits into your life.

Okay, back to the research findings. 

Hormones and Metabolism

Serum DHEA levels in both men and women are found to be lower with age, and this typically precedes menopause in women, and the general lowering of testosterone in men as they age. 

The connection to lower serum DHEA and then lower estrogen/progesterone in women, and testosterone in men, is linked to an increase in post meal fat storage, and a decrease in lipolysis of the fat tissue. 

In short, your fat cells are not functioning properly due to the decrease in these hormones, and that causes them to retain more fat, and have a lower propensity to burn fat. 

Furthermore, this propensity to accumulate more fat as a result of hormone imbalances, causes greater fat infiltration in organs like your liver, which can then cause health issues, and your pancreas, which can cause insulin resistance, and that can cause a host of issues from weight gain, to diabetes, and inflammatory related diseases. 

To sum it up, senescent cell accumulation increases everywhere in the body as we age, (this includes fat cells) simultaneously, key hormones decrease, causing hormone imbalances, and these two key factors cause fat cell dysfunction and misbehavior, and this dysfunction causes fat cells to become more stubborn, thus increasing their propensity for fat storage, and decreasing their propensity for fat burning (lipolysis). 

Okay, so we’ve learned from this research that if we can cut down on the accumulation of senescent cells through exercise, fasting, and supplementing with Senolytics (which also reduces risk of all other age related diseases), and gaining a more optimal hormone balance, we can negate some of the negative effects aging has on our body’s ability to burn fat. And if we can negate some of these factors, we can then more easily get back to “calories in vs. calories out” as the main factor affecting our ability to burn fat. 

Boosting DHEA

There is a direct link between a reduction of serum DHEA levels preceding a decrease in estrogen/progesterone in women, and testosterone in men. 

So, if there is substance to this correlation, this would mean that if serum DHEA levels were increased, estrogen/progesterone would increase in women, and testosterone would increase in men. 

This does in fact, appear to be the case for most men and women. 

To understand why, we must first understand what DHEA is. 

What is DHEA

DHEA, which stands for dehydroepiandrosterone, is a hormone produced by the adrenal glands. It is a precursor hormone, meaning it can be converted into other hormones such as estrogen and testosterone in the body.

DHEA plays a role in various physiological processes and is involved in the regulation of the endocrine system. It has been recognized for its potential influence on mood, energy levels, and overall well-being. DHEA levels tend to peak during young adulthood and gradually decline with age.

Supplementing with DHEA

DHEA has oral bioavailability, and is inexpensive, so it’s a pretty easy addition if trying to optimize hormones to reduce the effects of aging on the body. 

DHEA supplementation for women seems to be most effective starting at perimenopause and beyond, and for men, around the age of 40, when testosterone levels start to decline fairly significantly with age. 

Women typically benefit from 2.5mg of DHEA per decade of life, and men from 10mg per decade of life. 

So, a 50 year old perimenopausal woman would supplement with 10-15mg of DHEA, and a 50 year old man might supplement with 50mg of DHEA. 

Empathy provides clarity. 

The human condition is an incredible fascination of mine. 

On one hand, we’re all humans, all facing many of the same concerns, wants, and needs in life. 

On the other hand, when you peel back from those core concerns, wants, and needs of all humans, there is a tremendous amount of nuance. 

Different socioeconomic backgrounds, different problems in one’s daily lives, different education, upbringing, and so much more. 

This all shapes how we individually respond quite variably to many of the same issues and problems we all face. 

As I try to understand more and more about this amazing, eclectic mix of life we call the human condition, I’m making a conscious, concerted effort to look more closely at other’s perspectives, especially if I disagree with them on something, or we collectively, have a disagreement. 

Oftentimes, I will still walk away disagreeing with said individual, however, through trying to first better understand their worldview, I gain greater clarity on their perspective, on where they’re coming from, and why. 

By making more of an effort to make first acting with empathy my baseline, I find I gain greater clarity on my own thoughts, and on the world as well. 

Is this person who is upset or lashing out at me really just stressed out in their own life about certain things, and not dealing with it in a meaningful way? 

Is this causing them to react the way they are to me? 


And it’s still not an excuse to lash out at someone or take something out on someone, however, through first acting with empathy, you expose the “why” that might be causing them to do this. 

Through this clarity, you are more likely to deal with said individual in a better, more constructive manner, which is better for both of you.