Most of us can spot the outward signs of inflammation – be it a swollen, twisted ankle or a wound that just isn’t healing. But have you ever wondered why that pesky injury changes hues? Here’s the scientific explanation. Fluid, as well as red blood cells, leak into the injured area from blood vessels, which contributes to the redness (from the escaped red blood cells), and swelling from the escaped fluid. The swelling and inflammation can be attenuated by immediately applying a cold compress on the newly injured area. The appearance of the inflamed area changes hours after the injury to a black-blue appearance as the red blood cells rupture allowing the oxygen-carrying hemoglobin to become oxidized and turn a greenish-black color.
However, there’s much more to inflammation than meets the eye. This month’s Juvenon Health Journal covers recent work demonstrating the pitfalls of a chronic high fat diet on the microbial environment of the digestive system, which can result in systemic inflammation and disease.
Interestingly, scientists also explored the potential impact of berberine, a plant-derived nutrient that may offer important health benefits.
Simply put, the inflammation reaction to a traumatic injury – say a twisted ankle – is not unlike what occurs to the digestive system of someone on a high fat diet (HFD). Here’s the main difference. The HFD-induced intestinal inflammation results in a more generalized systemic inflammation, which harms all tissues of the body.
Beyond the Black and Blue: The Immune System at Work
Injury-inflamed tissue releases biomolecules (chemokines, cytokines), which in turn attract immune system cells (macrophages) to the site of injury. Serving as injury site commanders, the macrophages destroy and remove infectious agents, such as bacteria. They also remove injured tissue from the area to make space for the construction of new, healthy replacement tissue. Normally, this is a brilliant battle plan and goes off without a hitch. However, scientists now understand that a slew of problems can impact the fickle immune system’s response to actual or perceived injury.
Inflammation and High Fat Diet
It’s no secret that there’s a strong link between high fat intake, obesity and ill-health. Although this association varies from person to person (some are more resistant than others to the problems of a high fat diet and obesity), published studies clearly support the negative effects of excess fat. A recent study with rats fed a high fat diet clearly showed an increase in the leakage of bacterial contaminants called lipopolysaccharides (LPS) from the intestines into the blood stream. This was associated with increased levels of inflammatory substances produced by blood cells in response to the LPS. Prolonged feeding of the animals with a fat-enriched diet resulted in the pre-diabetic condition called metabolic syndrome, which may ultimately lead to diabetes. Below are the results of studies that reveal interesting findings regarding the inflammatory response triggered with a high fat diet.
Diet-Induced Change in Gut Microbiota
Our digestive system is a marvel in that it contains 10 times more cells, in the form of various families of bacteria than those cells comprising our entire body (100 trillion bacteria vs. 10 trillion cells comprising the body).
The enormous number of bacterial cells can be envisioned as an accessory organ, the microbiome. This accessory organ has an important function as it aids in the digestion of foods we eat, as well as providing a source of many essential vitamins and nutrients for maximum health.
Recent work has revealed the importance of both the quantity and the specific type or species of these microbes residing in our digestive system. Too many or too little bacteria can be harmful, but more importantly, the relative quantities of each species of bacteria can affect our health. A recent study with rats has shown that a diet high in fat alters the structure of the gut microbiota (bacteria forming the microbiome), and changes the type and ratio of the different species of bacteria living in our gut to one that is unhealthy and leads to disease. (See the “Summary of the Research Update” section of this journal.)
Briefly, the experiment involved four groups of mice fed one of the following diets for a period of 4 weeks. Group A was fed a normal chow diet (NCD), containing 10% fat. Group B was fed a NCD plus berberine (100mg/kg of body weight). Group C was fed a high fat diet (HFD), containing 60% fat. And finally, Group D was fed a HFD plus berberine (100 mg/kg of body weight).
Berberine Prevents Weight Gain
As expected, the results of this study showed a clear weight increase in those mice on the HFD alone, as compared to the NCD. However, those mice on the HFD plus berberine showed no weight gain as compared to the NCD mice. Additionally, those mice on the NCD along with berberine also had a relative weight loss, although slight (5-7%) as compared to the much larger weight loss (30-40%) with the berberine treated HFD mice. This is important as it gives hope to those people who eat a normal healthy diet – yet still struggle with weight. Berberine may help tip the scales.
Berberine Prevents Inflammation and Elevated Blood Glucose
The investigators carried the research further in order to determine quantities of glucose, as well as markers of inflammation present in the blood of the animals fed the four different diets. As expected, the mice fed the HFD alone had a significant increase in blood glucose, as well as an increase in several inflammatory molecules, as compared to the mice on the NCD. Those animals in the group fed HFD along with berberine had a no increase in blood glucose or in markers of inflammation. These results clearly show the positive health effects of berberine on important health parameters when a high fat diet is consumed.
Diet-Induced Change in Gut Bacteria
Based on previous studies, the investigators suspected that a diet high in fat may have a significant effect on the growth of some bacteria in the gut. Scientists deduced that this change may be responsible for the negative health effects of a HFD described above (increased inflammation, high blood-glucose). To determine whether this is a factor, they specifically examined the populations of various bacteria residing in the gut that were altered by the HFD.
Employing a sophisticated technique to examine bacterial populations residing in the gut, before and after the different groups of mice were fed the four diets, the investigators discovered that indeed the HFD did result in a change in the type of bacteria as compared to the NCD mice. Furthermore, mice fed the HFD with berberine showed a significant return to normal levels of those types of bacteria elevated in the mice fed the HFD. Specifically, certain types of bacteria were greatly decreased in the HFD fed mice, while the levels were brought back to normal in those mice fed the HFD plus berberine.
Interestingly, the bacteria that were decreased in response to the HFD are known to produce large amounts of short chain fatty acids, SCFAs (propionate, lactate, butyrate), molecules previously shown by investigators to protect the delicate cells lining the gut (see JHL vol 9, no 7). The investigators speculate the gut-protective effect of the SCFAs is what prevents the passage of bacterial contaminants into the blood stream from the intestines.
Berberine Protects the Gut from HFD-Induced Inflammation
The above results are interesting as they help explain why a high fat diet may increase the incidence of inflammation and disease. High fat appears to adversely affect the digestive system by supporting the growth of certain bacteria, thus upsetting the normal healthy ratio of bacterial species. Specifically, the HFD favors the growth of some bacteria at the expense of those bacteria producing nutrients, SCFAs, that function to increase the health of the intestinal lining. When this happens bacterial fragments (LPS, lipopolysaccharides), leak into the blood stream. Once in the blood stream, the immune system becomes activated as it recognizes these substances as foreign. The activated immune system produces inflammatory substances causing a more general inflammation throughout the body (systemic inflammation), leading to diseases such as diabetes.
Berberine is a plant alkaloid that has been shown in human clinical trials to help in weight control as well as to improve symptoms of type II diabetes. The results of studies presented here support a role for berberine as an anti-inflammatory agent acting on the intestines to improve the integrity of the cells lining the digestive system, and preventing the transport of inflammatory bacterial agents from entering the blood stream. This mechanism may at least partly explain why berberine is an effective nutrient for controlling type II diabetes and excess body weight, as both conditions are aggravated by inflammation.
Berberine has also been shown to increase the production of catalase, as several international studies, including two conducted in 2006 and 2010, demonstrate. When taken in supplements, berberine can increase the production of catalase in the body’s mitochondria. Catalase is a crucial enzyme and super-antioxidant. Increasing its production has been shown to reduce mitochondrial dysfunction to promote anti-aging.
Take Home Message
Although the above study was carried out with animals, previous clinical studies indicate many of the results reported likely apply to humans. For optimum health, aim for a diet low in fat and sugar with lots of fruits, vegetables, whole grains, fish and lean meat. However, berberine may help those who do fall off the wagon on occasion, as well as those who maintain a healthy diet, but because of genetics and metabolic issues have difficulty maintaining a healthy weight.
answers your questions.
question: I am a 50-year-old woman who has always been very careful to maintain my weight with a healthy diet and exercise. Over the last few years my weight has been creeping up on me. I exercise, try very hard to eat healthy, and I keep my caloric intake to a minimum. Is there anything else I can do to help keep off the pounds?-JT
answer: Exercise, especially aerobic exercise including walking, running and swimming, is exceptionally good for maintaining a healthy weight. As we age, we do put on weight as a consequence of metabolic changes. This occurs in both men and women and is partly due to hormonal changes.
You mention in your letter that you are following a healthy diet, which I assume includes lots of low glycemic foods including fruits, berries, vegetables, legumes, as well as lean meat and fish as a source of protein. Try to keep saturated fats and junk food to a minimum, and when possible substitute olive oil (first cold pressed virgin oil) for vegetable oil. Two nutrients that may help with healthy metabolism and weight control are berberine, a plant alkaloid, and resveratrol, a polyphenol.
There is evidence that these two nutrients can improve fat burning and glucose metabolism. Resveratrol, for example, increases the production of catalase. Why is that important? Catalase, an enzyme, is vital to your good health. As a super antioxidant, catalase protects your cells. To give you an idea of how powerful this enzyme’s anti-oxidant properties are, consider that in only one second a single catalase enzyme can convert up to 40 million molecules of hydrogen peroxide free radicals into water and oxygen. By supplementing your healthy, low-fat diet with berberine, you may increase the production of catalase and reap the benefit of its cellular protection. Combine that with aerobic exercise for a balanced approach to maintaining healthy weight and youthful energy.
Dr. Benjamin V. Treadwell is a former Harvard Medical School professor and member of Juvenon’s Scientific Advisory Board.
A group of investigators from Shanghai Tong University in China were intrigued by the effectiveness of the plant-derived alkaloid berberine on improving the symptoms of type II diabetes and prevention of obesity in spite of its rather poor absorbance from the gut into the blood stream after oral administration. The investigators were aware of the use of berberine over the years for the treatment of bacterial diarrhea. In turn, they hypothesized that berberine may act on pathogenic bacteria to improve the health of the gut and this may be one of the mechanisms involved in its positive effects on obesity and diabetes in humans.
The experimental design to test this hypothesis was to feed rats for a four-week week period, four different diets.
- Group A: This group of rats received a normal chow diet (NCD) containing 6% total fat.
- Group B: These rats were maintained on a diet of high fat (HFD) containing 60% saturate fat.
- Group C: This group received a diet containing NCD with berberine (100 mg/kg body weight).
- Group D: This group received a diet containing HFD with berberine.
At the beginning and termination of the experiment animals were weighed and blood samples were taken for analysis of markers of inflammation, blood glucose and the blood binding protein lipopolysaccharide (LBP). Furthermore, fecal samples were taken for analysis and determination of the different types of bacterial populations and their relative amounts. This latter procedure required a sophisticated analysis examining a specific region (V3 region) of the 16S ribosomal RNA genes that is unique to each species of bacteria.
As expected, the results showed an increase in body weight (30% – 50%) and elevated blood-glucose with the HFD as compared to the NCD rats. Additionally, there was an increase in markers of inflammation and LBP, the latter being a good indicator of leakage of bacteria from the gut into the blood stream. Interestingly, those animals on the HFD containing berberine did not gain weight nor did their blood-glucose levels and markers of inflammation increase relative to the NCD animals. Furthermore, the indicator of blood-borne bacterial contamination, LBP, remained the same as the NCD rats. Although the NCD rats that were fed berberine did not show any changes in the blood markers examined relative to NCD rats alone, there was a slight decrease in body weight (10%) relative to the NCD rats.
The most exciting and potentially important single result from this study is that showing a diet high in fat does have a significant effect on the gut micro biota (type of bacteria residing in the gut). Investigators believe this result supports their hypothesis of how berberine may be acting to prevent obesity and disease in HFD rats. Their result shows that those animals on a high fat diet have a significant decrease in the amount of healthy bacteria populations. These healthy bacteria are known to produce and secrete into the gut specific short chain fatty acids (SCFAs, such as propionate, acetate, butyrate). These SCFAs were shown to have a protective effect on the epithelial cells lining the gut and maintaining the integrity of the gut lining. The loss of these bacteria (preventable by berberine) can compromise the gut allowing bacterial fragment to cross the gut vascular barrier and enter the blood stream.
Read abstract Here
This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.