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Herbal Treatments for Non-alcoholic fatty liver disease (NAFLD)

Herbal Treatments for Non-alcoholic fatty liver disease (NAFLD)
By Renata Trister DO

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver injury. There is also strong association to other conditions, such as obesity, diabetes, cardiovascular diseases, and metabolic syndrome. The exact pathology of NAFLD is not fully understood, but seems connected to insulin resistance, lipid metabolism dysfunction, oxidative stress, and inflammation. NAFLD is one of the leading causes of chronic liver disease in both developed and developing countries. Although it is considered a somewhat benign form of chronic liver injury, without proper treatment and lifestyle modifications, about 20% of NAFLD patients can advance to cirrhosis and liver cancer. Recently, the use of herbal treatments for NAFLD has received attention due to their low side effects, and proven therapeutic benefits. The use of wolfberry, garlic, resveratrol (from grape seeds), and milk thistle seem to be most promising.

Lycii fructus (wolfberry, goji berry)

Wolfberry or goji berry is the fruit of plant Lycium barbarum of the family Solanaceae. These berries have been used in traditional Chinese medicine for centuries to support the liver and the eyes. The polysaccharide in the goji/wolfberry (often referred as LBP) appears to be the most active portion. Studies show that LBP has many effects, including antioxidant effect, immunoregulation, neuroprotection, control of glucose metabolism, and anti-tumor activity. Clinical trials also found that intake of goji berry juice increases the number of lymphocytes and levels of interleukin-2 and immunoglobulin G. LBP also was found to increase the serum levels of antioxidants. In the liver, studies show that treatment with LBP inhibited proliferation and induced apoptosis in hepatoma cells, suggesting possible anti-tumor activity of LBP.

Garlic, or Allium sativum, is a species in the onion genus Allium. It has a very long history (over 6,000 years) in culinary and medicinal uses all over the world. A recent paper reported a liver protective effect of dietary consumption of fresh garlic. Garlic attenuates abnormal lipid profile through AMP-activated protein kinase (AMPK) pathway. The use of raw garlic along with the diet modifications improves insulin resistance, oxidative stress, and lipid metabolism.

Resveratrol is a substance extracted from red grapes. It is one of the most well-documented and accepted herbal medications in the world due to its tremendous effect against oxidation and inflammation. In recent years, many groups have found the very promising phytochemical properties of resveratrol in the treatment of NAFLD. Treatment with resveratrol can lead to the suppression of lipogenic genes in the liver. This effect was further supported by the studies in which treatment with resveratrol diminished oxidative stress and inflammation.

Milk thistle
Silymarin is a derivative of plant milk thistle (Silybum marianum). Thousands of papers have been published on the antioxidative, and hepatoprotective effects of silymarin. In the liver cells, the beneficial effects of silymarin include antioxidative effects, direct/indirect effects on inflammation and fibrosis, as well as modulation of metabolic pathways. The anti-inflammatory effects of silymarin are due to its interference with NF-κB–controlled transduction cascade. A recent basic study showed that crude extract of Silybum marianum has a powerful anti-inflammatory role in the treatment of steatohepatitis.

The pathology of NAFLD is very complex and not yet understood. It is attributed to multiple events, from insulin resistance to apoptosis. Goji berry derived LBP, garlic, resveratrol, and milk thistle are the most promising herbal remedies that can target some of the pathological changes of NAFLD development.



The fibrous pericardium is attached to the posterior surface of the sternum by the superior and inferior sterno-pericardiac ligaments (sternopericardial ligaments); the upper passing to the manubrium, and the lower to the xiphoid process.
The bronchopericardial membrane is a group of connective tissue in the posterior mediastinum, forming strong fiber bands that connect the root of the lung, the bifucration of the trachea and that radiate across the wall of the inferior vena cava and to posterior part of t he tendinous center of the diaphragm.


How To Begin Using Herbal Supplements Dr. Renata Trister DO

How To Begin Using Herbal Supplements

Dr. Renata Trister DO

Starting your journey into herbal supplements can be challenging. Exciting headlines of the latest studies are everywhere, but often leave us baffled. There is an overwhelming amount of products, brands, and preparations. Which ones are safe? Who can you trust? Which should you buy and try?

To the herbal novice, starting to take herbal supplements can be a confusing and scary endeavor because there’s a lack of regulated, clear communication to consumers on ingredient quality, effectiveness, and proven health benefits. However, when taken properly, herbal supplements can support many conditions, such as stress reduction, weight management, immune system support and combating depression. The key is to keep it simple and stay safe.

Where To Start

Although it may be tempting to go after the “latest and greatest” herb or supplement, in my opinion, the herbs that deserve the most attention are a bit more conservative. The following is a list of herbs that not only have the largest amount of clinical data, but also have hundreds of years of use and are viewed as sacred by multiple generations of herbalists in many cultures.
Adaptogens are non-toxic plants that help the body resist various stressors – physical, chemical or biological. These herbs and roots have been used for centuries in Chinese and Ayurvedic healing traditions. They help the body adapt to stress and to exert a normalizing effect upon bodily processes (adapt to internal/external stressors, fight fatigue, increase stamina but also mitigate anxiety and stress). Adaptogens benefit mental function, feelings of calmness and may help fight fatigue and enhance physical activity by lowering oxidative damage and increasing energy production in cells. Panax Ginseng, Rhodiola, Schisandra Berry, Eleuthero or Siberian Ginseng and Turmeric are the most revered herbal adaptogens. These herbs have a wide range of uses and come with very few downsides. They also can be used together or in various combinations for a synergistic effect.
Panax Ginseng (Panax ginseng) has been used in traditional Chinese medicine for centuries. Ginseng has beneficial antioxidant and anti-inflammatory properties. Some test-tube studies have shown that ginseng extracts and ginsenoside compounds could inhibit inflammation and increase antioxidant capacity in cells. It can help reduce inflammatory markers and help protect against oxidative stress. Panax ginseng is an amazing adaptogen. It also seems to be beneficial in the control of blood glucose in people both with and without diabetes.

Rhodiola (Rhodiola Rosea) also is an adaptogen and acts in non-specific ways to increase resistance to stress, without disturbing normal biological functions. This herb grows at high altitudes in the arctic areas of Europe and Asia, and its root has been used in traditional medicine in Russia and the Scandinavian countries for centuries. Studies of Rhodiola rosea’s medicinal applications have appeared in the scientific literature of Sweden, Norway, France, Germany, the Soviet Union and Iceland. Rhodiola rosea is still widely used in Russia as a tonic and remedy for fatigue, poor attention span, and decreased memory; it is also believed to make workers more productive. In Sweden and other Scandinavian countries it is used to increase the capacity for mental work and to boost general strength and vitality.

Numerous studies of rhodiola in both human and animal models have indicated that it helps prevent fatigue, stress, and the damaging effects of oxygen deprivation. Evidence also suggests that it acts as an antioxidant, enhances immune system function, and can increase sexual energy.

Schisandra (Schisandra chinensis) is widely used in traditional Chinese medicine. This berry growns East Asia, where it is called Wu Wei Zi, or “five flavor fruit,” because the berries possess all five basic flavors: salty, sweet, sour, pungent, and bitter. Schisandra has been used as a supportive treatment for coughs, indigestion, diarrhea, flu and premenstrual syndrome. It is traditionally used to support your body’s capacity to handle stress, sustain energy and concentration. It is also known to support healthy liver function, which can reduce the signs of stress and inflammation of the skin.
Siberian ginseng (Eleutherococcus senticosus) Eleuthero or Siberian ginseng, grows in mountain forests and is native to eastern Asia including China, Japan, and Russia. Traditional Chinese Medicine has used eleuthero for reducing lethargy, fatigue, as well as for increasing endurance and resilience to various stresses. A compound found in eleutherococcus called eleutheroside appears to reduce the severity and duration of herpes simplex 2 infections. It is also a great herb to take to reduce the duration of the common cold (especially when combined with an herb called andrographis).
Turmeric (Curcuma longa) is actually a very common spice that spans centuries of use in many cultures. Botanically related to ginger turmeric has tremendous anti-inflammatory properties. One of the most comprehensive summaries of turmeric benefits was published by the respected James A. Duke, Phd.
Reviewing some 700 studies looking at turmeric’s health benefits, Duke concluded that turmeric appears to outperform many pharmaceuticals in its effects against several chronic, debilitating diseases, and does so with virtually no adverse side effects.
Here are some of the diseases that turmeric has been found to help prevent or alleviate:
Alzheimer’s disease: Over 50 studies on turmeric’s effects in addressing Alzheimer’s disease were analyzed. The reports indicate that extracts of turmeric contain a number of natural agents that block the formation of beta-amyloid, the substance responsible for the plaques that slowly obstruct cerebral function in Alzheimer’s disease.
Arthritis: Turmeric contains over two dozen anti-inflammatory compounds, including six different COX-2-inhibitors (the COX-2 enzyme promotes pain, swelling and inflammation; inhibitors selectively block that enzyme). Curcumin – the component in turmeric most often cited for its healthful effects – is a multifaceted anti-inflammatory agent. Turmeric can be used to alleviate occasional aches and pains as well as an herbal alternative to ibuprofen.
Always Be Safe
Botanicals are medicine. They can have powerful physiological effects. I strongly suggest you consult with your doctor before starting an herbal regimen. Experience and education are key.
Herbal supplements are regulated by the FDA. These regulations improved somewhat when the FDA introduced mandatory Good Manufacturing Practices (GMP) in 2007. GMP is a set of requirements and expectations by which dietary supplements must be manufactured to guarantee ingredient identity, purity, and composition. GMPs aim to prevent misleading claims, the addition of too much or too little of a dietary ingredient, the possibility of contamination (by pesticides and heavy metals such as lead, bacteria, etc.), and the improper packaging and labeling of a product. Companies who adhere to this set of guidelines are starting to produce more effective and reliable herbal remedies. However, the active ingredient level of an herb is still a recommendation rather than a requirement. MediHerb upholds the highest quality of medicinal herbs, creating both single herbs and multi-herb blends giving consumers the ability to find mixes of herbs for specific needs. They adhere to standards that are above and beyond FDA/GMP’s requirements.


Zonulin and Leaky Gut By Renata Trister DO

Zonulin and Leaky Gut
By Renata Trister DO
An amazing discovery has dramatically altered our view of gut permeability and its impact on a wide range of conditions such as cancer, autoimmune disease, inflammation and food sensitivity.


Zonulin is a protein that moderates the permeability of tight junctions between cells of the wall of the digestive tract. It essentially opens up the spaces between the cells of the intestinal lining. This occurs normally so that nutrient molecules can get in and out of the intestine. In leaky gut, these intercellular spaces open up too much allowing larger protein molecules to enter the bloodstream. Once in the bloodstream these proteins can elicit an immune response. After this occurs, the body is primed to react to these proteins every time they enter the bloodstream. Intestinal contents, bacteria can also leak in creating inflammation.

Zonulin Triggers:

The two most powerful triggers are gluten and gut bacteria in the small intestine. Gliadin (a class of proteins present in wheat and several other cereals within the grass genus Triticum) causes zonulin levels to increase both in those people who have celiac disease and those who do not. As the zonulin level rises, the seal between the intestinal cells diminishes, opening up spaces between cells. This is called “leaky gut”. The immune system views these particles in the bloodstream as foreign invaders and will subsequently mount an immune response. This can lead to food sensitivities. Furthermore, this immune activation can damage the intestinal cells and the gut becomes more permeable and more inflamed. Over time the microvilli that line the intestines become damaged. The villi seen in a healthy gut lining are almost completely lost in celiac patients, greatly reducing the surface area and impairing nutrient absorption.

Top Causes of Increased Zonulin and Development of Leaky Gut:

Overgrowth of harmful organisms, like bacteria or yeast in the intestine
SIBO = small intestinal bacterial overgrowth
Fungal dysbiosis or candida overgrowth
Parasite infections
Gliadin in the diet (gluten containing foods)
A study published in the Scandinavian Journal of Gastroenterology in 2006 clearly showed that gliadin can affect zonulin even in people without the gene for celiac. Based their results, it was concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.

Elevated Zonulin Levels And Leaky Gut Are Also Associated With The Following:
Inflammatory Bowel Disease
Crohn’s disease
Type 1 Diabetes
Multiple Sclerosis

Miscommunication between innate and adaptive immunity, exposure to environmental triggers, genetic predisposition, and loss of intestinal barrier function secondary to the activation of the zonulin pathway by food and environmental triggers all seem to be key in the pathogenesis of inflammation and autoimmunity.

How to check your zonulin levels:

There are a couple of ways to check your zonulin levels. The first is a simple blood test to check for levels of protein expression in the blood.
A second option is the lactulose or mannitol test, which assesses the gut permeability by measuring the levels of both compounds in urine after they have been ingested. The patient drinks a premeasured amount of lactulose and mannitol. The degree of intestinal permeability or malabsorption is reflected in the levels of the two sugars recovered in a urine sample collected over the next 6 hours.

So to summarize, zonulin is an important modulator of gut permeability. It has strong associations with several disorders of the gut. This protein was first described in the 2000s and is therefore very new. Genetic markers, diagnostic tests are still being developed.



By Renata Trister DO
Your liver is one of the largest organs in your body, and it
performs a vast array of metabolic functions.
Additionally, the liver plays a role in regulating blood sugar,
breaking down damaged blood cells, and removing toxins from our
bodies. Because of these important functions, a sluggish or
diseased liver can take its toll on your overall health.
There are many steps you can take to support your liver and ensure
its proper function. One of the simplest things you can do is to
avoid or limit toxins. This includes alcohol, processed sugar and
sweets and over-the-counter pain relievers. Diet also plays a huge
role in the health of our liver. The following is a list of natural
remedies that can be used for liver support.
In Chinese medicine, Qi is your vital life force and is responsible
for the harmonious “flow” of energy in our bodies. Because of its
role in healthy circulation, the liver is largely responsible for
maintaining Qi. Additionally, Chinese medicine believes that the
best time to support your liver is first thing in the morning.
There are studies that show the benefit of consuming acidic
substances for the liver. Apple cider vinegar has been shown to
have a protective effect on the liver and lower oxidative stress.
Citrus juices, like lemon, also have benefits, including anti-
inflammatory and antioxidant capabilities.
Drinking these acidic drinks early in the morning may increase the
beneficial effects. Wake up your liver in the morning by adding a

couple TBSP of apple cider vinegar and a squeeze of lemon to a
cup of warm water.
 Milk thistle benefits work by drawing toxins out of the body
and protecting the liver from damage. This herb is used for
liver support, milk thistle is a powerful liver cleanser. It helps
rebuild liver cells while removing toxins from the body that
are processed through the liver. Silymarin, which is derived
from the milk thistle plant, has been used in traditional
medicine as a natural remedy for diseases of the liver because
of its potent antioxidant activity.
 Oregon Grape Root for its ability to stimulate liver function
and relieve congestion. This herb also helps improve the flow
of bile through our bodies, which promotes efficient blood
 Beet Root is shown to have protective and anti-carcinogenic
benefits for the liver. Beets are widely available at the
grocery store and can also be juiced. Supplements containing
beet root powder are also available.
 Dandelion is an herb that has been noted for purifying and
protecting the liver from oxidative stress and injury.
Dandelion is available in tea, tincture and can be eaten fresh
in salads.
 Alfalfa Sprouts are vitamin-rich shoots that help to reduce
the accumulation of cholesterol in the liver.

 Cichoric acid, found in the herb Echinacea purpurea, has
demonstrated promise for its preventive effects liver lipid
metabolism disorders in obesity.
Castor oil packs have been used to promote circulation of the
blood and lymphatic drainage.
Historical textbooks list castor oil as one of the oldest ways to
support health with citations dating back to 1550 BC in Egypt,
thousands of years in India and China, and Europe.
Castor oil and its major constituent ricinoleic acid, an unsaturated
omega-9 fatty acid, has been researched for analgesic, anti-
inflammatory, laxative, and uterine relaxation effects. Specifically
castor oil has been shown to increase the levels of T-11
lymphocytes in the top layers of the skin, increase prostaglandin
E2, and activate the EP3 prostanoid receptor. Increase in T-11
lymphocytes is hypothesized to support immunity.
The heat from a castor oil packs increases blood flow and may
improve oxygenation to target tissues. Castor oil also activates the
VR1 receptor similarly to capsaicin, and this may account for its
analgesic effects.
Castor oil has a lipid structure that easily passes through the skin’s
surface. As castor oil moves through the lymph system, it
stimulates a healthy flow of lymph fluid. This flow is essential to
removing waste materials from the body. Castor oil contains
ricinoleic acid, which is easily absorbed into the liver. Ricinoleic
acid is a powerful anti-inflammatory agent that also provides
significant pain relief.

Castor oils packs are typically placed on top of the liver or on top
the uterus. The former supports liver health, while the latter
supports reproductive health. Castor oil packs should be avoided
while trying to become pregnant, and during pregnancy.
Wool flannel large enough to cover the liver.
Organic, cold pressed castor oil.
Plastic wrap.
Hot water bottle.
Towel that you don’t mind getting dirty.
Storage container for wool flannel once finished with pack (a
mason jar or plastic bag).
Warm water on the stove until almost boiling. Lay towel on bed or
Stretch plastic wrap over towel and lay out piece of wool flannel.
Saturate the flannel in castor oil (you want it fully saturated, but
not dripping).
Once water is warm, fill water bottle.
Place wool flannel and plastic wrap on top of liver or abdomen.
Cover as much of the flannel as possible with plastic wrap.
Lie down on towel and place warm water bottle on top of liver.
Relax for 20-30 minutes or longer. Repeat this procedure as often
as desired.
You may also enhance your castor oil pack with essential oils for a
relaxing, aromatic experience.



By Renata Trister DO

Brief History

The low FODMAPs diet is an elimination type diet that has become first line of dietary therapy recommended for patients suffering with IBS. 
This plan was developed by Australian dietitian Sue Shepherd and the researchers at Monash University in the late 1990s. Much research was done on this subject and in the early 2000s the Monash university team developed a well-defined and structured diet plan specifically formulated for patients with IBS. 

What is FODMAPs?

The acronym FODMAPs stands for Fermentable Oligosaccharides Disaccharides Monosaccahrides and Polyols. These are complex names for different short chain sugars found in foods. The F in Fermentable means that intestinal bacteria can consume these sugars producing gas through their digestive processes. The rest of the acronym just lists the names of the different types of short chain sugars. These fermentable sugars are found in various carbohydrate rich foods, such as starchy foods (certain grains, breads and cereals) as well as in some fruits, vegetables and dairy. These short chain sugars are not very well absorbed by the body. Rather than being absorbed in the small intestine, these small chain sugars travel to the large intestine. The large intestine contains trillions of bacteria that use these undigested sugars for food. When these bacteria consume these sugars, they produce gas. Patients with IBS have sensitive intestinal lining and experience this with bloating and pain. Furthermore, the presence of undigested FODMAP sugars in your colon attracts water, causing loose stools and diarrhea. Reducing the number of FODMAPs in the diet, can decrease gas, pain and fluid in the large intestine of patients with IBS. A low FODMAPs diet has also been shown to reduce the amount the amount of histamine. Histamine is a natural substance, a biogenic (resulting from the activity of living organisms such as, fermentation) amine that is present in many foods and is produced by human cells with a wide array of functions. Histamine is a neurotransmitter, it has a role in allergic reactions, often associated with causing itching, redness, swelling, cough or rash. Histamine regulates sleep and aids in digestion by playing a role in stomach acid secretion. The accumulation of histamine and the inability of the body to completely degrade it may play a role in the pain symptoms many IBS sufferers experience. Studies have shown that following a low FODMAPs diet plan can have an 8-fold decrease in histamine levels in some IBS patients.

Where are FODMAPs found?

Examples of foods high in each of the FODMAPs.

Oligosacchrides/ Fructans: Artichokes, Garlic, Leek, Onions, Green Onions, Shallots, Wheat, Rye, Barley, Fructo-oligosaccharides (FOS) found in Agave Syrup and Asparagus. Galacto-Oligosaccharides (GOS) found in Beans, Lentils, Chickpeas.

Disaccharides/ Lactose: Dairy products such as Milk, Ice Cream, Yogurt, Soft Cheeses (such as cream cheese ricotta, cottage, brie).

Monosacchrides/ Fructose: Apples, Mangos, Pears, Watermelon, Honey, High-Fructose Corn Syrup.

Polyols: Found in stone fruits such as Apricots, Nectarines, Pears, Plums, Prunes, as well as in sugar alcohols sorbitol, mannitol, xylitol, maltitol and isomalt. These sugar alcohols are often found on ingredient labels of many prepackaged and processed foods.

The list is not complete. The best way to begin your low FODMAPs protocol is to discuss this with your physician and use the Monash University FODMAPS app.

What does the low FODMAP diet involve?

The Low FODMAP Diet has two phases.

Phase 1

During first phase of the Low FODMAP Diet all high FODMAP foods are strictly eliminated for 4-6 weeks. Using the Monash FODMAPs app is important for this process. The symptom response during this period should be monitored and noted.

Phase 2

During the second phase foods that were restricted in the first phase are reintroduced gradually. This is where the type and amount of FODMAPs that can be tolerated by the individual are identified.

Expected Outcomes

According to a study published in the Journal Gastroenterology, about 3 out of 4 people with IBS had their symptoms ease after starting a low-FODMAP diet and felt the most relief after 7 days or more on the plan. Success rates vary and depend on the type of IBS a patient has.


How Bacteria Influence Food Cravings and Weight.

How Bacteria Influence Food Cravings and Weight.
By Renata Trister DO
Literature Review

Studies on the gut-brain axis suggest that the bacteria in your gut could strongly influence your food choices.
97 percent of women and 68 percent of men report having cravings for foods they are trying to avoid. Cravings are thought to be a combination of psychological and physiological factors and are a major barrier to weight loss and health.

Recent evidence suggests that gut microbes might play a significant role in influencing cravings. Given that microbes evolved with us and depend on the foods we eat for survival, it follows that these organisms influence our eating preferences to improve their own chances of survival.

The enteric nervous system (found in the gut) is connected to the central nervous system (the brain and spinal cord) via the gut-brain axis. This term is more of a description of the interrelationship between the intestines and the brain. The two are connected by the circulatory system and the lymphatic system.
The enteric nervous system is also connected directly to the brainstem via the vagus nerve. The vagus nerve acts as a superhighway for communication between the gut and the brain and is the longest nerve cell in the autonomic (unconsciously controlled) nervous system. Studies on the vagus nerve found that vagal blockade can lead to marked weight loss, while vagal stimulation triggers excessive eating in rats.

Different microbes have different food preferences. Bacteroidetes have a preference for particular fats; Prevotella likes carbohydrates; Bifidobacteria prefer dietary fiber.
All of these microbes require these foods to grow and reproduce. Studies have shown that a low concentration of nutrients triggers increased virulence in many microbes as a survival mechanism. Virulence is the ability of a particular microbe to cause damage to the host. For many human-associated microbes, the production of virulence toxins is altered by the detection of simple sugars and other nutrients.

When bacteria metabolize foods, they produce various metabolites. Microbial metabolites include many neuroactive agents that are small enough to penetrate the blood-brain barrier. Studies on chocolate cravings have found that even when eating identical diets, people who crave chocolate have different microbial breakdown products in their urine than people who do not crave chocolate.

Short-chain fatty acids (SCFAs), metabolites produced from the fermentation of dietary fiber in the GI tract, are able to modify the expression of genes in cells throughout the body, including brain cells.
Other microbially derived molecules are able to mimic hunger or satiety hormones. Your body normally secretes hormones like ghrelin (to stimulate your appetite) and peptide YY (to signal that you are full). Many gut bacteria are able to manufacture small peptides that mimic these hormones. Helicobacter pylori is a great example. Eradication of Helicobacter pylori is accompanied by an array of metabolic and hormonal changes in the host. Weight gain following H. pylori eradication is a poorly understood phenomenon and probably results from an interaction between multiple factors. Ghrelin, a peptide hormone secreted by the stomach, is involved in the regulation of food intake and appetite and may account for some of these changes. Studies have demonstrated that H. pylori infection suppresses circulating ghrelin levels. Gastric expression of ghrelin, also suppressed by H. pylori, clearly increases following eradication. Weight gain following H. pylori eradication may be attributable to changes in plasma and gastric ghrelin. As wide use of antibiotics continues, many people now no longer have Helicobacter pylori present in their microbiome.

Microbes therefore can interfere with human appetite by either directly mimicking satiety and hunger hormones or indirectly inducing this autoimmune response.

Bacteria also produce neurotransmitters. More than 50 percent of your body’s dopamine and 90 percent of your body’s serotonin are produced in your gut, along with about 30 other neurotransmitters. These molecules are critical for signaling between cells of the nervous system. Dopamine and serotonin are involved in the regulation of eating behaviors.

An increasing number of studies are showing connections between the gut microbiota with stress, depression and anxiety. In 2004, an experiment showed that mice raised in sterile conditions with no gut microbes had an exaggerated hypothalamic–pituitary–adrenal (HPA) axis response to stress. The effect was reversed by colonization with Bifidobacterium species. Furthermore, a study published in 2012 found that germ-free mice prefer sweets and have a greater number of sweet taste receptors.

Microbial diversity may determine how easily host behavior can be changed. Obese individuals tend to have lower microbial diversity than individuals of a healthy weight. This may partially explain why people who are overweight tend to have difficulty with cravings.

To support your microbiome you may try the following:

Several strains of Bifidobacterium and Lactobacillus have been shown to improve anxiety- and depression-like eating behaviors.

Prebiotics are foods that selectively feed certain beneficial microbes. Try fermentable fiber found in foods like plantains, onions, garlic, and sweet potatoes. Supplementing with inulin or resistant starch is also an option.

Nutrient density
Eating a clean diet rich in green vegetables, healthy proteins and fats supports the health of both your body and the microbiome.


Vitamin D and Inflammatory Bowel Disease

Vitamin D and Inflammatory Bowel Disease
By Renata Trister DO

Literature Review

A relationship between vitamin D and Inflammatory Bowel Diseases (IBD) has recently been proposed. Vitamin D has several important actions beyond the bone maintenance. Vitamin D also exerts various effects on the immune system. Vitamin D deficiency has been implicated in the development of IBD such as Crohn’s Disease (CD). Current research also suggests a role for vitamin D in modulating some IBD complications, including osteopenia, colorectal neoplasia, and depression.
Vitamin D is well established as a regulator of calcium homeostasis. Recently, literature has linked vitamin D to a number of other conditions, including cancer, cardiovascular disease, and autoimmune diseases such as multiple sclerosis, diabetes mellitus, and
Crohn’s disease (CD). The incidence of Crohn’s disease, in general, appears to rise with increasing distance from the equator. Those residing in temperate climates have less exposure to sunlight, which is responsible for up to 95% of vitamin D production in humans. Vitamin D deficiency is found in 22 to 70% of patients with CD and has been proposed to play a key role in its pathogenesis.

Vitamin D deficiencies are common in patients with IBD. Normal levels of vitamin D are approximately 30 ng/mL. Levels between 20 and 30 ng/mL are considered insufficient, and anything below 20 ng/mL is considered deficient. The prevalence of vitamin D deficiency in inflammatory bowel disease (IBD) varies in different studies.
Laboratory experiments in various mice models have also shown that animals are more susceptible to colitis and that such colitis can be treated by vitamin D supplementation. These findings suggest, that there is at least a significant component of vitamin D level perhaps contributing to the development of IBD; vitamin D deficiency is not purely a consequence of prolonged, undertreated IBD or bowel damage, but is rather an artifact of immune dysregulation.

A growing body of literature has linked disease severity to low vitamin D levels. For example, a comparison of 3000 people with Crohn’s disease or ulcerative colitis and examined vitamin D levels showed that there is a gradation in the risk of surgery in people who had normal, insufficient, and deficient levels of vitamin D. People who had insufficient levels of vitamin D (20-30 ng/mL) had a higher risk of surgery and hospitalization, and people with levels lower than 20 ng/mL had an even higher risk of surgery and hospitalization.
Vitamin D can be considered a hormone with a number of effects on the immune system that are responsible for mediating susceptibility to infections and perhaps malignancy. Studies have suggested that vitamin D levels may be important in how patients respond to pathogens. Studies have linked low vitamin D levels with an increased risk of cancer, particularly colon cancer, in people with IBD. Low vitamin D levels are also linked to a higher risk of Clostridium difficile infection.

It is important to further evaluate the relationship of vitamin D deficiency and IBD to determine which one comes first. Prolonged bowel damage can cause IBD, with growing evidence and laboratory data suggesting that vitamin D is a potential mediator of several immune responses, the connection between Vitamin D levels and subsequent development of autoimmune conditions should not be disregarded. It is important to understand the role of vitamin D in the treatment of IBD itself, and not just for the treatment of vitamin D deficiency. We also need to better understand the optimal dose of vitamin D supplementation, and whether there are factors such as genetics that influence response to such supplementation. It is also important to define what the optimal vitamin D level should be in patients with IBD, and whether there should be a different adequate level when looking at inflammation. There is also growing evidence supporting the relationship between the gut microbiome and Vitamin D axis in autoimmunity. Bacterial induced modifications in Vitamin D metabolism can have vast effects on Vitamin D levels and Vitamin D Receptor signaling. Probiotics promote Vitamin D Receptor expression and its antimicrobial effects. This can be beneficial in treating colonic inflammation. Proper Vitamin D balance may restore healthy gut microbiome and decrease inflammation.




The sequential metabolic processes which convert inactive pro-hormone (Vitamin D) to Active form called Vitamin D endocrine system. The key elements of this system are photo-conversion, the liver, the kidney as an endocrine gland, the vitamin D receptor (VDR) and the vitamin D binding protein (VDBP).

Vitamin D is then transported to the liver where it’s hydroxylated by an enzyme (CYP2R1) to produce 25(OH)D (25-hydroxyvitamin-D). 25(OH)D is then transported to the kidneys where it’s hydroxylated by another enzyme (CYP27B1) to produce 1,25OH2D (1,25- dihydroxyvitamin-D). Many cells outside the kidneys contain VDR and express CYP27B1 (the enzyme that catalyzes 25(OH)D to 1,25(OH)2D).

The vitamin D receptor (VDR), nuclear receptors, transduce hormonal signals from the immediate environment and transactivate genes in response to these signals .VDR has been identified in 37 different tissues throughout the body (including the nucleus of phagocytic cells of the immune system)

The most important function of 1,25(OH)2D is to bind to the VDR nuclear receptor and mediate the transcription of DNA, triggered by signaling proteins

The effects of 1,25(OH)2D are pleiotropic;

Most dividing cell types, normal and malignant, can express VDR and respond to 1,25(OH)2D.

VDR- activated genomic expression mediates many tissue-specific biological effects. Classical effects (e.g., calcium transport and bone health, etc.) and Non-classical, extra-skeletal effects (cell differentiation, central nervous system, skin/hair, immune regulation, hormone secretion, etc.).

In addition to the classical VDR-mediated genomic pathway, 1,25(OH)2D also has been shown to elicit rapid responses that occur within a few minutes after hormone treatment and are considered too rapid to be explained by a VDR-mediated genomic pathway. These  rapid responses are mediated by a direct action of 1,25(OH)2D on the plasma membrane of target cells stimulating a signal transduction pathway involving the rapid opening of voltage- sensitive Ca2+ channels and activation of protein kinases.

VDR are present in most cell types of the immune system, particularly in antigen- presenting cells (APCs) such as monocyte, macrophages and dendritic cells. The influence of 1,25(OH)2D on the immune system is one of its most important roles. In general, the innate system is enhanced and the adaptive system is inhibited by 1,25(OH)2D. The innate system is suppressed by 25-OH  and the adaptive system is stimulated by 1,25(OH)2D.

1,25(OH)2D activates the VDR to express antimicrobial peptides (AMPs) such as cathelicidin and beta defensins which attack pathogens. Recently, 1,25(OH)2D-induced autophagy has been reported (autophagy contributes to anti-aging, antimicrobial defense, and tumor suppression). VDR immune system regulation also involves cell proliferation, differentiation and apoptosis. The VDR is also expressed in both B and T white blood cells (lymphocytes)

In monocytes and macrophages (innate immune system), synthesis of 1,25(OH)2D from 25(OH)D promotes an antibacterial response to infection. Monocytes sense pathogen-associated molecular patterns (PAMPs) by utilizing pattern-recognition receptors (PRR), such as toll-like receptors (TLRs). Induction of CYP27B1 occurs following PAMP-sensing by TLR2/1. The inflammatory cytokine interferon γ (IFNγ) also stimulates expression of CYP27B1 by macrophages. As a result, 1,25(OH)2D production is increased in response to a pathogen immune challenge.

1,25(OH)2D modulates the adaptive immune system by inhibiting dendritic cell maturation, reducing T helper (Th) cells, and shifting Th1/Th17 cells to the Th2 and T regulatory pathways. In addition, 1,25(OH)2D inhibits Th1 cytokines that support cell-mediated immunity and promotes Th2 cytokines that support humoral immunity (antibodies circulating in bodily fluids). The immune response is heavily dependent on the vitamin D endocrine system, performing a balancing act of inflammation/anti-inflammation.

There is no consensus on the definition of vitamin D deficiency or insufficiency and authorities haven’t agreed on the significance of low 25(OH)D.

The Institute of Medicine (IOM) report emphasized that the current measurements, or cut-off points, of sufficiency and deficiency of 25(OH) D in use by laboratories have not been set using rigorous scientific studies. The IOM report emphasized that the current measurements, or cut-off points, of sufficiency and deficiency of 25(OH) D in use by laboratories have not been set using rigorous scientific studies. They suggest that since no central authority has determined which cut-off points to use, reports of deficiency and lab ranges may be skewed and numbers overestimated. Most importantly, 25(OH)D may not always reflect the level of 1,25(OH)2D (the active metabolite).

Researchers in Denmark measured the baseline serum 25(OH)D and total cholesterol levels of 182 fair-skinned and dark-skinned subjects; and studied the effect of UV radiation on their serum 25(OH)D levels. They found the amount of serum 25(OH)D produced was determined by the amount of cholesterol in the skin, not on skin pigmentation. Most importantly, skin pigmentation doesn’t negatively affect vitamin D status. Persons with dark skin compensate for low 25(OH)D by rapidly converting it to the active 1,25(OH)2D metabolite, thus allowing them to maintain adequate vitamin D status. Matsuoka et al concluded that while racial pigmentation has a photo-protective effect, it does not prevent the generation of normal levels of active vitamin D metabolites. The concern about dark skin and vitamin D deficiency appears to be misplaced. ample opportunities exist to form vitamin D (and store it in the liver and fat) from exposure to sunlight during the spring, summer, and fall months even in the far north latitudes.

Our bodies have mechanisms for preserving the vitamin D we acquire during the summer; which have evolved to stabilize and maintain serum levels of vitamin D in environments with variable vitamin D availability. The Vitamin D Binding Protein (DBR) optimizes and stores 25(OH)D for later use; it also binds 1,25(OH)2D, as well as the parental vitamin D itself. DBP sequesters vitamin D sterols in the serum, prolongs their serum half-lives, and provides a circulating store of vitamin D to meet transient periods of deficiency. In so doing, DBP helps to prevent the development of severe vitamin D deficiency.

Clothing is a barrier to ultraviolet radiation but this is an issue only for people who cover themselves from head to toe (e.g., woman who wear a burka may not be exposed to sufficient sunlight). It takes relatively little sunlight exposure to acquire adequate stores of vitamin D and few people wear enough clothes to prevent that from happening. Ten to 15 minutes of sunlight or daylight exposure to a small area of skin (e.g., the forearm or face, etc.) twice a week (without sunscreen) supplies all the vitamin D necessary for health. Evidence for a beneficial effect of vitamin D supplementation in cancer is lacking. The findings of a large prospective study in 2008 do not support the claim that vitamin D is associated with decreased risk of prostate cancer; in fact, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease. The Women’s Health Initiative (WHI) Calcium plus Vitamin D Supplementation Trial, published in November 2013, concluded that after an average of 11 years, calcium and vitamin D supplementation did not decrease colorectal cancer incidence.

Adequate vitamin D is essential to prevent rickets, but adequate calcium is equally important; if either calcium or vitamin D is deficient, bone health suffers. Rickets is rare in the developed world; however, children in developing countries, who usually photosynthesize enough vitamin D from sunlight, develop rickets if poverty prevents them from eating enough calcium rich food. Studies found rickets occurs in sunny countries due to poor calcium intake and is cured with increased calcium ingestion.

Osteoporosis is a bone disease characterized by a decrease in bone mineral density and the appearance of small holes in bones due to loss of minerals. Vitamin D is an important factor in maintaining bone health to avoid osteoporosis. Precise maintenance of the physiologic levels of both extracellular and intracellular ionized calcium is essential to life; 1,25(OH)2D maintains calcium homeostasis between blood, cells and bones by stimulating calcium absorption from the intestines, reabsorption in the kidneys, and resorption in bones. 1,25(OH)2D up-regulates VDR in the small intestine, which then transcribes genes that shuttle calcium and phosphorus through the intestinal epithelium. However, mucosal response and calcium/phosphorus absorption is dependent on a competent VDR and elevated 1,25(OH)2D reduces VDR competence. Thus, calcium and phosphorus absorption may be inhibited if VDR function is impaired by elevated 1,25(OH)2D. This is illustrated by a study of Crohn’s patients with elevated 1,25(OH)2D and low bone mineral density which concluded that treatment of the underlying inflammation would improve metabolic bone disease.

Vitamin D supplementation is ill- advised above a threshold of 30ng/ml 25-D. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin-D status is reported in a wide range of disorders. It would be wiser to seek reasons underlying the low vitamin-D level, such as inflammatory processes. Elevated 1,25(OH)2D leads to bone loss. When levels are above 42 pg/ml 1,25(OH)2D stimulates bone osteoclasts. This leads to osteoporosis, dental fractures and calcium deposition into the soft tissues: lungs, breasts, muscle bundles, kidneys. An earlier study warned, “Vitamin D is a toxic compound, and excessive amounts can cause soft-tissue calcification. There is a narrow leeway between the amount required and that initiating tissue damage.” Combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health. This significant evidence regarding bone loss should motivate medical practitioners and researchers to measure both 25(OH)D and 1,25(OH)2D to determine vitamin D status.

Autoimmune diseases: An alternate hypothesis posits a bacterial etiology in which a persistent intracellular infection causes a cytokine release that induces signals to T cells and B cells, and the antibodies they produce (to the intracellular invader) include some that attack human proteins, as well as target the pathogens. In other words, when an innate immune system is forced to respond to a persistent infection, the resulting cascade of chemokines and cytokines will also stimulate an adaptive response. Vitamin D has a positive effect on autoimmune disease because it reduces symptoms via immune system suppression. For example, abnormal T cell reactivities in MS patients were reduced with vitamin D supplementation; serum 25(OH)D levels after 12 months were increased to 71.7 ng/ml ± 39 ng/ml. Vitamin D inhibits pro-inflammatory processes by suppressing the enhanced activity of immune cells that take part in the autoimmune reaction.

Exposure to ultraviolet light, especially UV-B wavelengths, can impair immune responses in animals and humans. Thus, seasonal variation can have an impact on the immune response; in the summer, when vitamin D3 is highest, 1,25(OH)2D down-regulates the immune system. Reduced immunity following exposure of skin to UV radiation may explain the positive latitude gradient measured for a number of autoimmune diseases (decreased incidence of disease with residence at lower latitudes). Unfortunately, some researchers believe immunosuppression is the best form of treatment for autoimmune disease. Vitamin D proponents have failed to recognize the immunosuppressive effect of elevated 25(OH)D and to acknowledge that immunosuppression is contraindicated in the presence of infection. As a result of vitamin D immunosuppression inflammation, clinical disease markers and symptoms of autoimmune disease are reduced but this doesn’t treat the underlying cause and relapse is common.

Verway et al. wonder, “Is a specific pathogen responsible for disease or rather is a dysregulated immune response generated against a complex microbial population? Why would immune-suppressive drugs be efficacious if the primary defect is an immune deficiency?”

The suppressed immune system enables chronic infection and inflammation. Intracellular bacteria are able to persist and proliferate in host phagocytes, successfully compete for nutritional resources and displace commensal organisms from their niche. The result is chronic illness.

There is a positive role for vitamin D in bone health but not in other health outcomes. Genetic findings in those predisposed to longevity cast doubt on whether low levels of vitamin D cause age-related diseases and mortality. A study concluded that vitamin D supplementation did not reduce knee pain or cartilage volume loss in patients with symptomatic knee osteoarthritis. Subjects supplemented with high doses of vitamin D saw no improvement in serum lipids, HbA1c, or HS-CRP. Supplementation did not significantly reduce the incidence or duration of upper respiratory tract infections. In a study of older adults, the decline in physical performance and strength was not associated with 25(OH)D.

Vitamin D deficiency or insufficiency can occur in certain situations. Genetic defects in the VDR may result in vitamin D deficiency; a number of mutations have been identified that lead to hereditary vitamin D resistance. Disorders that limit vitamin D absorption and conditions that impair conversion of vitamin D into active metabolites may cause deficiency. Sick or elderly people who rarely go outdoors and have poor diets are also at risk.

Decreases in vitamin D levels are a marker of deteriorating health. Inflammation is the common factor between most non-skeletal health disorders and low 25(OH)D concentrations.

Increases in 25(OH)D have no effect on inflammatory processes or on disorders at the origin of these processes.


Immune system. Brief Review. By Jon Trister, MD

The Immune System, brief review.

To defend as form invaders  body has two immune systems:

The first defense system is an innate immune system we are born with. This is a  first defense against any foreigners-microbes, viruses, funguses. This is antigen non-specific defense mechanisms which respond to invaders immediately or within several hours after exposure to every foreigner. Cells associated with innate immune system are Macrophages, Dendritic cells and  B-lymphocytes.

The second defense system is an adaptive immune system (acquired) immunity refers to antigen-specific defense and require  several days to become protective and are designed to react with and remove a specific antigen. Adaptive immunity is the immunity one develops throughout life. Cells associated with adaptive immune system are T- and B-Lymphocytes

 One of the function of the innate  immune system is an APC ( antigen presentation cells)-is an identification, isolation  of the antigen-specific protein -epitope-actual portions or fragments of an antigen that react with receptors on B-lymphocytes and T-lymphocytes, as well as with free antibody molecules) and presentation it in the from of complex : MHC I/epitope  or MHC ii/epitope on the surface of the APC ( Macrophages, Dendritic cells, B-Lymphocytes).Epitope is a fragment of the antigen which will provide adaptive immune system a specific  information about invader ( antigen).Without ability to perform this function as an APC innate immune system will be unable to “educate” adaptive immune system about structure of the antigen.

Polysaccharides antigens( 3-4 sugar residuals)  usually have many epitopes but all of the same specificity.

Proteins antigens (5-15 amino acids )usually have many epitopes of different specificities.

Immune responses are directed against many different epitopes of many different antigens of the same microbe.

The body recognizes an antigen as foreign when epitopes of that antigen bind to B-lymphocytes and T-lymphocytes by means of epitope-specific receptor molecules having a shape complementary to that of the epitope.

  MHC molecules

MHC-I molecules are made by all nucleated cells in the body

MHC-I presents epitopes to T8-lymphocytes; MHC-II presents epitopes to T4-lymphocytes.

MHC-I molecules are designed to enable the body to recognize infected cells and tumor cells and destroy them with cytotoxic T-lymphocytes or CTLs.

CTLs are effector defense cells derived from naïve T8-lymphocytes.

MHC-I molecules are made by all nucleated cells in the body; bind peptide epitopes typically from endogenous antigens; present MHC-I/peptide complexes to naive T8-lymphocytes and cytotoxic T-lymphocytes CTL.

 MHC-II molecules are made by antigen-presenting cells or APCs, such as dendritic cells, macrophages, and B-lymphocytes; bind peptide epitopes typically from exogenous antigens; and present MHC-II/peptide complexes to naive T4-lymphocytes or effector T8-lymphocytes that have a complementary shaped T-cell receptor or TCR

Exogenous antigens enter antigen-presenting macrophages, dendritic cells, and B-lymphocytes through phagocytosis, and are engulfed and placed in a phagosome where protein antigens from the microbe are degraded by proteases into a series of peptides. These peptides are then attached to MHC-II molecules that are then put on the surface of the APC.