Categories
Health

10 Conditions That Cause Chronic Fatigue

With our hectic lifestyles and less than optimal health habits, feeling like you have no energy is a modern day epidemic. For an ever-increasing number of individuals, however, feeling tired

Sleep

Sleep is essential to our body. It allows the brain to consolidate memories and thoughts, and to work more efficently. Poor or inadequate sleep can wreak havoc on your mental health by disrupting your circadian rhythm, and this, in turn, causes fatigue and brain fog just like chronic fatigue syndrome.

Check out our Sleep Optimization Checklist for a list of useful tips on how to improve your sleep quality.

Diet

The most common cause of fatigue is a poor diet. A good diet is not necessarily about losing weight, it’s about eating healthy food and feeling better. In this highly advanced and globalized society where you can buy and eat all kinds of delicious foods from all over the world, we are getting fatter and sicker compared to previous generations. Here’s why…

a. Nutritional deficiencies

Iron deficiency (often found with vegetarians and vegans) and lack of vitamin B12 can cause anemia, a common pathology where the blood cannot supply enough oxygen to the body due to a lack of important nutrients.

High-potassium-foodLow potassium and magnesium levels are also associated with low energy and fatigue. Low potassium can be easily treated by eating bananas: one banana contains around 425 mg of potassium [1], so eating two bananas a day for a week can easily replenish the potassium stores of the body.

Magnesium is a key nutrient. Over 300 enzymes require the presence of magnesium ions, including all enzymes synthesizing ATP (the primary source of energy in cells) as well as DNA and RNA. It is, unfortunately, becoming harder and harder to find in today’s highly-processed food. Because of this, the only method to replenish the magnesium ions in the body is to use a magnesium supplement. It’s essential to get a good magnesium supplement – most of the commercial magnesium brands contain “cheap” inorganic forms for economic reasons. These are usually magnesium oxide, magnesium chloride or sulfate, which have very low bioavailability and are often used as laxatives. The most effective magnesium forms are malate, glycinate, orotate, and taurate. We recommend the malate salt which is especially effective for pain and fatigue. A less expensive option is magnesium citrate.

b. Excessive carb intake

99carbsOther than nutritional deficiency, an excessive intake of carbohydrates is a very common cause of chronic fatigue.

First of all, we need to remember that the “modern” Western diet is full of carbohydrates, particularly refined carbs such as sugar, corn syrup, fructose, as well as refined flours, grains, and starches. Not all carbs are immediately used by the body. Excessive glucose (sugar) gets stored in the body for future use as glycogen and fat. However, there is one thing that all carbs do: they make the body secrete insulin, and insulin decreases plasma levels of large amino acids that would ordinarily compete with tryptophan for transport (particularly in the blood-brain barrier), therefore increasing tryptophan availability.

Tryptophan and its metabolite, serotonin, have a complex role in the brain, but the two things they are most known for is regulating mood and hunger. Low levels of serotonin[2] have been associated with depression (even though this is recently being disputed) while high levels (especially its precursor, tryptophan[3]) have been correlated with fibromyalgia and chronic fatigue.

It should also be noted that an insulin spike is followed by a crash, which can further exacerbate symptoms of mental fatigue and depression. And that’s not all!

A group of researchers at the University of Bordeaux found that when rats were given a choice between a sugar substitute and intravenous cocaine, 94% of them chose the sugar substitute.[4]

While the research on cardiovascular disease in the last fifty years has been focusing mainly on the dangers of fats, new research reveals that carbs are actually more dangerous to health than fats. A study showed that a high-carb diet increased blood fats level more than a high-fat diet![5]

If you crave carbohydrates as your primary source of energy, it’s time to cut them back. But the brain needs glucose to function, how can glucose be produced without carbs?

Luckily, this is not really a problem for the human body. If you think about it, the early human diet was made almost entirely of protein and fats. As a matter of fact, the body can produce glucose from proteins through a process called gluconeogenesis. [6]

low-carb-foods

While this idea of a low carb diet [7] may seem a crazy, it actually goes back to the 1920s [8]. Originally developed to reduce symptoms of epilepsy, (back when anticonvulsant drugs did not exist), the ketogenic diet has helped millions people all over the world lose weight and overcome their chronic fatigue as of today.

Without getting too technical, the ketogenic diet forces the body to burn fats rather than carbohydrates. In this process, ketone bodies are created, and they replace glucose as the body’s primary source of energy. When there is a high blood level of ketones the body goes into a ketosis state, which leads to a reduction of the frequency of epileptic seizures.

But that’s not all! Without carbs to get in the way, the body starts burning fats at a much higher rate, and this helps those in overweight in shedding excessive fats and reach the desired weight.
For more information check the keto subreddit.

Parasites

Even though parasites may make you think of Third World countries, they are still fairly common in civilized nations. Tapeworms, hookworms, pin worms, liver flukes, giardia, these are just a few of the parasites that cause disease in humans.

intestinal parasites

Symptoms of parasitic infestation include:

  • fatigue and lethargy
  • abdominal pain and swelling
  • fever
  • vomiting
  • diarrhea
  • malnutrition and anemia
  • loss of appetite and blood

The severity of these symptoms depends on the type of parasite, the number of parasites, and the site of the infestation. Most infections are asymptomatic, especially in the early stages. Parasitic infections are usually treated with benzimidazoline drugs like mebendazole (Vermox) and albendazole (Albenza) while protozoan parasites (like giardia) are treated with nitroimidazole antibiotics like metronidazole (Flagyl) and tinidazole (Tindamax).

“Colon cleanse” supplements have never been proved to work, and they should not be used as a primary treatment but only to augment the efficacy of antiparasitic drugs.

Eating good amounts of garlic, papaya, and black pepper, and taking a zinc supplement, may reduce the severity of the infestation.

Thyroid

thyroidHypothyroidism is a common condition caused by the thyroid not producing enough thyroid hormones (T4 and T3). This generally happens for two reasons: Iodine deficiency or Hashimoto’s thyroiditis.

Iodine deficiency is the most common form, and it is caused by an inadequate amount of iodine in the diet. This type of hypothyroidism is fairly widespread in second and third world countries. One of the ways in which governments have tried to prevent this is by promoting the use of iodized salt (table salt with additional potassium iodide).

Hashimoto’s thyroiditis, on the other hand, is an autoimmune disease in which the immune system sees the thyroid cells as an enemy and attacks them. It is one of the most common causes of hypothyroidism in the United States.

But fatigue is not only a symptom of hypothyroidism: it can, (even though it’s less prevalent), also be a symptom of hyperthyroidism, the opposite of hypothyroidism.

If your metabolism is too slow (or too fast), or if you can’t stand hot (or cold) temperatures, you should check TSH, T4, and T3 levels through a blood test.

It is a good idea to supplement the building blocks of thyroid cells: iodine and selenium (200 mcg each). Iodine can be supplemented with a potassium iodide supplement or Lugol’s iodine. Selenium should be supplemented in the selenomethionine form since sodium selenite is a pro-oxidant, which is not something we generally want (unless you have cancer).[9]

Medications

A fairly common side effect of some medications (especially those that act on the brain) is fatigue. If you are taking supplements, it’s also a good idea to stop taking them one at a time for a couple days and see if there is an improvement.

In general, the worst offenders are antidepressants, antipsychotics, antihistamines, and beta blockers. Please consult a medical professional before you stop taking a psychiatric medication.

That being said said, here is a list of medications commonly associated with fatigue, sedation and brain fog:

  • Antidepressants: mirtazapine (Remeron), citalopram (Celexa), paroxetine (Paxil), trazodone (Desyrel), mianserin (Norval), amitriptyline (Elavil), imipramine (Tofranil), clomipramine (Anafranil) etc.
  • Antipsychotics: all of them
  • Antihistamines: diphenhydramine (Benadryl), promethazine (Phenergan), hydroxyzine (Atarax)
  • Beta-blockers: all of them
  • Benzodiazepines: alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan), clonazepam (Klonopin)

Adrenals

adrenal-hormonesThe adrenal glands are two small glands that sit on top of the kidneys. They produce a variety of hormones, including cortisol, adrenaline, and aldosterone, through a process called steroidogenesis.

The adrenals produce three types of hormones: mineralocorticoids, glucocorticoids, and androgens.
Mineralocorticoids help blood pressure regulation and electrolyte balance.
Glucocorticoids — including cortisol and corticosterone — regulate the immune system as well as metabolism.
Androgens are steroids that get converted to fully functional sex hormones in the gonads and other target organs.

There are a number of diseases that affect the adrenal glands. An overproduction of cortisol causes Cushing’s syndrome and a deficiency of cortisol causes Addison’s disease. Cortisol and adrenaline are implicated in the stress response (“fight-or-flight response“). Too much cortisol promotes stress and anxiety and not enough cortisol causes chronic fatigue.

But why do the adrenals stop working properly? Two common reasons are either stress or a over-consumption of drugs that affect the adrenal glands, like caffeine and amphetamines.

About caffeine and stimulants…

Seriously, who doesn’t love a cup of coffee in the morning? It tastes great, helps you wake up and stay focused, it’s full of antioxidants, and protects your liver — this “liquid gold” can truly be a lifesaver when used correctly. But an excessive or poorly timed use of coffee and other caffeine sources, on the other hand, can stress your adrenal glands and disrupt your sleep cycle (which by itself increases cortisol).

As a rule of thumb:

  • avoid taking caffeine after 5 pm
  • limit intake of caffeine to no more than 300 mg a day (a cup of coffee usually contains between 60 to 100 mg of caffeine)
  • do not mix caffeine p0wder or coffee with other stimulants

The same principles more or less apply to stimulants. They may seem like a good idea when you’re feeling exhausted and unmotivated, but if the fatigue is a symptom of a chronic condition they end up doing more harm than good.

Excessive use of stimulants may lead to burn-out, psychosis, and neurotoxicity.

Inflammation

disease caused by chronic inflammationInflammation is part of the process that begins as a response of the body to harmful stimuli. Inflammation is usually caused by an infection, but that is not always the case – in some cases, the harm done by years of an unhealthy lifestyle (through smoking, drug abuse, over-consumption of alcohol, or an inadequate diet), can produce a chronic inflammatory state.

Chronic inflammation – whether caused by infection or a bad lifestyle – is associated with heart disease, muscle loss, cancer, depression (and other mood disorders), shortened lifespan, and autoimmune diseases.

Methylation cycle

The methylation cycle is a biochemical pathway that regulates a number of bodily functions, including detoxification, the immune system, energy production, and mood. Explaining the methylation cycle is a bit out of the scope of this article, and I’ll address it in a future one.

What is important to know is that individuals generally fall into two categories: under-methylators and over-methylators. Typically these genetic differences in methylation are discovered by genome testing, like 23andme.

Here you can read more about the methylation cycle, how it works and how is it linked to chronic fatigue and poor mental performance.

Conclusion

In the end, there are many conditions that cause or mimic chronic fatigue. As chronic fatigue is a relatively complex and still pretty unknown syndrome, it is a good idea to test for all the conditions we just explained, before giving up to the diagnosis.

As a matter of fact, there are other conditions that may cause this syndrome – like hypogonadism (low testosterone levels), or high blood ammonia – but we left those out to cover them in detail in future articles.

Have you enjoyed the article? Do you feel like you may have one of this conditions? Leave us a comment!

References   [ + ]

Categories
Cognitive Health Health Recovery

9 Supplements To Counteract The Negative Effects of Alcohol

Despite clinical proof that alcohol has detrimental effects on the human body, even more so than certain illegal substances, it still remains one of the world’s most readily available and favorite intoxicants. Alcohol has been a mainstay in nearly every society for thousands of years, and its commonality leads some people to not even recognize it as a drug. From sporting events to celebrations with family, it’s likely you will toss back a few drinks on occasion.

However, even moderate alcohol use can carry negative side effects. Consequently, many people seek supplements that will help mitigate some of the deleterious effects on the human body caused by consumption. Whether it’s for an occasional night on the town or more frequent use, or even for recovering from years of alcoholism, there are natural herbs, supplements, and nootropics that have been proven effective for harm reduction with alcohol use.

  • Before consuming any substance along with alcohol, be careful to check for any known interactions. Some nootropics have not been extensively studied and may possess undocumented interactions.
  • GABAergic nootropics like phenibut should be avoided because they can boost the effect of alcohol by producing similar effects of intoxication. It is generally not a good idea to mix alcohol with other depressants.
  • Many ADHD medications that contain amphetamine salts or methylphenidate can delay the onset of alcohol effects leading to increased consumption and potential heart problems.

Dihydromyricetin (DHM)

dihydromyricetinDihydromyricetin, a flavonoid, increases metabolism of both alcohol and its primary metabolite, acetaldehyde, by increasing key enzymatic action. In addition to ridding your body of these toxins, it has demonstrated effectiveness at blocking alcohol at the neurological level by binding to GABA receptors in place of alcohol. [1] While this compound theoretically shows promise for hangover prevention, many clinical studies need to take place before it’s classified as a safe supplement for human use.

Milk Thistle

Milk_thistle_flowerMilk Thistle, used as a natural medicine for over 2000 years, can accelerate the regeneration of liver cells and reduce fatty liver deposits that build up with alcohol use. It has been hypothesized that milk thistle increases the rate of protein synthesis in the liver, allowing it to more readily repair itself from alcohol-induced damage. [2] Milk thistle contains silibinin, which is thought to be the main active constituent of the plant.[3] Many users take milk thistle as a daily supplement, but it can also be consumed after a night of drinking to aid the liver in detoxification.

N-Acetylcysteine (NAC)

NAC is a nutritional supplement that is able to increase levels of the endogenous peptide glutathione [4], an important antioxidant. If you take NAC before a session of drinking, it can potentially reduce the oxidant side effects of alcohol. [5] It can also decrease the acetaminophen toxicity induced by alcohol. [6]
NAC also has anti-addictive properties.

Emoxypine

emoxypineEmoxypine (also known as Mexidol) is an antioxidant drug that is molecularly similar to pyroxidine, a form of vitamin B6. Emoxypine was first synthesized in Russia, where it is used in the medical field for its anxiolytic, nootropic, neuroprotective, and anti-inflammatory effects, among others. [7] Emoxypine possesses general antioxidant properties, but also can specifically counteract the negative effects of alcohol. It displays therapeutic effects against health issues caused by chronic alcohol use and acute intoxication. In experiments, emoxypine administration reversed the learning deficits caused by chronic alcohol use in rats. [8] Emoxypine also lowers lipofuscin amounts in the cerebrum, much like piracetam. In terms of acute alcohol use (one night of heavy drinking), emoxypine significantly reduces the physical and mental feelings of intoxication that alcohol produces, specifically improving muscle coordination and mental clarity.[9]

Tauroursodeoxycholic Acid (TUDCA)

TUDCATUDCA is a bile acid that is found in trace amounts within humans. However, additional supplementation may be beneficial for those who are attempting to recover from alcoholism. TUDCA is used in some countries to treat gallstones and cirrhosis of the liver, but it is not FDA approved for this purpose in the United States.[10] TUDCA has been demonstrated to increase healing rates in unhealthy livers, specifically ones that have been damaged by alcohol. [11] TUDCA should not be consumed before drinking, as it carries the possibility of potentiating liver damage. Rather, TUDCA should be supplemented after drinking, or could be used on a regular basis by former alcoholics who wish to promote healing in their liver. [12]

Ashwagandha

HER-ASH01-2Ashwagandha is an herbal supplement that contains various chemicals known collectively as withanolides. These chemicals have been found to be effective at decreasing social anxiety when paired with alcohol, and ineffective threshold doses of either appear to be highly effective when combined. [13] However, the social disinhibition produced by alcohol alone may make this combination unnecessary for some users. Another use of this popular supplement is to aid in quitting alcohol consumption altogether. Indeed, alcohol cessation cold turkey can lead to an increase in anxiety. Ashwagandha has been clinically proven to reduce spikes in anxiety from abstinence. [14]

Agmatine

Agmatine is an amino acid and neurotransmitter derived from the amino acid, L-Arginine. It has been noted for its positive effects on neuropathic pain and drug addiction. Agmatine appears to reduce symptoms of alcohol withdrawal and dependence, such as anxiety and tremors. [15] [16] One note of caution: Agmatine is known to be a gastro-protective agent but when co-ingested with alcohol it can enhance ulcer formation. [17]

Piracetam

piracetam_structure_500pxWhile moderate alcohol use does not typically cause damage to the brain, cognitive functions are significantly impaired following the consumption of alcohol, and can continue to be impaired the next day or so after it is consumed. Nootropics that possess cholinergic mechanisms are potentially effective in improving cognition against alcohol-induced impairment. [18] Alcohol consumption increases neuronal lipofuscin, which contributes to age-related neurodegenerative disorders. [19] Piracetam and other racetams, in general, inhibit the accumulation of neuronal lipofuscin, counteracting neurodegeneration. [20]

L-Theanine

Matcha
Matcha is a Japanese green tea with a very high content of L-Theanine

The amino acid theanine, which is naturally found in green tea, is another important supplement that may provide liver protection from alcohol consumption. In one study, mice treated with L-theanine prior to alcohol consumption had lower ethanol concentrations in their blood after one hour compared to mice that were administered only alcohol. [21] This implies that L-Theanine could help the body recover faster from the negative effects of alcohol. (Consequently, this also implies Theanine could also decrease the duration of alcohol’s “positive” recreational effects.) Alcohol use typically impairs the antioxidant capabilities of hepatocytes (liver cells), and L-theanine has been found to restore the antioxidant capabilities of these cells. [22]

Conclusion

Alcohol has maintained its status as society’s drug of choice throughout history. As a result, it will continue to be used extensively and excessively by many despite its potential health risks. Those who are well armed with the knowledge of the aforementioned substances can use them to counteract and overcome the neurological and physical difficulties caused by alcohol consumption.

At the end of the day, supplements and nootropics can only do so much to prevent the negative effects of alcohol. A cautious and responsible approach to alcohol consumption is ultimately the most important component of using alcohol safely.

References   [ + ]

1. Dihydromyricetin As A Novel Anti-Alcohol Intoxication Medication (2012)
2. Biochemical effects of the flavonolignane silibinin on RNA, protein and DNA synthesis in rat livers. (1986)
3. Silibinin protects OTA-mediated TNF-alpha release from perfused rat livers and isolated rat Kupffer cells. (2009)
4. Alcohol and thermally oxidized pufa induced oxidative stress: role of N-acetyl cysteine (2004)
5. Antioxidant therapy attenuates deficient bone fracture repair associated with binge alcohol exposure (2011)
6. Clinical course of repeated supratherapeutic ingestion of acetaminophen.
7. Comparative Analysis of the Anxiolytic Effects of 3-Hydroxypyridine and Succinic Acid Derivatives (2015)
8, 9. Antioxidant Mexidol. The main neuropsychotropic effects and the mechanism of action. mechanism of action. (2009)
10. The clinical profiles of primary biliary cirrhosis with a suboptimal biochemical response to ursodeoxycholic acid. (2011)
11. Endoplasmic reticulum stress inhibition protects steatotic and non-steatotic livers in partial hepatectomy under ischemia-reperfusion. (2010)
12. Toxicity of ethanol and acetaldehyde in hepatocytes treated with ursodeoxycholic or tauroursodeoxycholic acid. (2004)
13. Effect of Withania somnifera Dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats. (2008)
14. Evaluation of Ashwagandha in alcohol withdrawal syndrome (2012)
15. Effects of agmatine on ethanol withdrawal syndrome in rats. (2000)
16. Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats. (2010)
17. Investigation on the mechanism involved in the effects of agmatine on ethanol-induced gastric mucosal injury in rats. (2000)
18. Can nootropic drugs be effective against the impact of ethanol teratogenicity on cognitive performance? (2001)
19. Chronic alcohol consumption induces lipofuscin deposition in the rat hippocampus. (1986)
20. The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal: a quantitative study. (1991)
21. Effects of theanine on alcohol metabolism and hepatic toxicity. (2005)
22. L-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes. (2012)
Categories
Health

6 Supplements to Boost Your Immune System

Immune system functioning is something that is often taken for granted. Even when one is not feeling sick, the immune system is working every hour of every day by neutralising cancerous growth, clearing wastes from the body, and fighting developing infections[1]. Certain supplements have the potential to provide a boost to your immune system function for fighting off illnesses caused by infections and for supporting general well-being.

Zinc

zincThe beneficial effects of zinc for symptoms of the common cold were first documented 30 years ago[2]. Since then, a modest body of literature has formed which supports the efficacy of zinc as a mild palliative aid for cold symptoms. Prophylactic administration of zinc (to prevent cold) has not been substantiated[3]. Further studies are needed as the current data are not fully conclusive.

Zinc modulates various components of both the innate (e.g. neutrophils, macrophages)[4] and adaptive (e.g. B- & T-lymphs)[5][6] immune systems.

Effectiveness

A 2015 Cochrane review of 16 therapeutic trials (n = 1387) found that administration within 24h of cold onset at a dose of over 75 mg per day had the following effects[7]:

  • Zinc significantly reduced the duration of cold symptoms by a mean difference of -1.03 days
  • Zinc had no effect on the severity of cold symptoms.
  • Individuals who took zinc were about half as likely to be symptomatic after 7 days of treatment, were less likely to develop a cold, less likely to be absent from school, and were less likely to be prescribed antibiotics (note: although antibiotics should not be prescribed for the common cold as it is caused by a virus, they are nevertheless frequently given due to patient insistence.).

Although the authors noted high heterogeneity within the data, these data appear to corroborate general findings from the literature. Zinc appears to be mildly effective for reducing symptoms of the common cold.

Formulations

Zinc is available in many salt forms. The most common over-the-counter formulations are zinc oxide, zinc acetate, and zinc gluconate[8]. Other formulations vary in bioavailability, with zinc monomethionine being the most absorbed. The amount of ionic zinc content seems to be correlated to therapeutic efficacy[9], however, the acetate and gluconate salts have been most studied.

The usual dosage ranges from 4.5 to 24 mg of elemental zinc taken every 1 to 2 hours during waking hours as cold symptoms persist[10]. The regimen is typically continued for 5 to 14 days or until symptoms subside.

Cautions

High doses (≥100 mg) of or prolonged exposure (≥10 years) to zinc may be unsafe[11], and has been linked to adverse sequelae such as prostate cancer. Be aware of elemental zinc content in multivitamins. Pregnant or breastfeeding women should limit their zinc intake to less than 40 mg/day.

As a caution, zinc may interfere with the absorption of certain drugs[12], such as quinolone and tetracycline antibiotics, as well as other mineral supplements, such as calcium or iron. Notify your doctor and pharmacist if you are taking zinc. Zinc should be taken 2 hours before or 6 hours after quinolone & tetracycline antibiotics.

Side effects are relatively mild and limited. Bad taste and nausea are frequently reported[13].

There is a concern that doses higher than 40 mg per day may interfere with copper absorption, leading to anaemia[14]. One study has tested the effects of long-term coadminstration of zinc & copper; through 6 years of supplementation no significant adverse effects were reported[15].




Garlic

garlicGarlic is a culinary herb that has been largely investigated for its benefits on cardiovascular health, which stem from modest reductions in blood pressure and cholesterol levels[16]. In addition to these helpful effects, garlic may also have an immunostimulating effect.

The active constituent in garlic is a compound called allicin, which has been shown to promote the activity of various components of the immune system, evidenced by enhanced phagocytosis, lymphocyte proliferation, and inhibition of immunosuppressive processes, among other mechanisms. Allicin has also demonstrated intrinsic antimicrobial activity demonstrated in vitro.

Formulations & Dosage

Garlic can be consumed in a variety of forms. In general, the recommended allicin intake is 2 to 5 mg per day[17]. The following dosages approximate this amount. Be advised that various formulations may vary in allicin content and pharmacologic properties [18]. Further information about various formulations and intake can be found here.

  • 2 to 5 g of fresh garlic (cut, not crushed & uncooked[19])
  • 0.4 to 1.2 g of dried powder
  • 2 to 5 mg of oil
  • 300 to 1000 mg of extract

Warnings

Increased garlic intake should be avoided in individuals with a bleeding disorder (e.g. haemophilia or other coagulopathy) or planned surgery within 2 weeks[20]. Because allicin has been shown to inhibit platelet aggregation and TxA2 synthesis, individuals consuming large amounts of garlic are at an increased bleeding risk. Exercise caution if you are taking «blood thinners» such as warfarin or aspirin and consult your doctor and pharmacist before use.

Individuals with diabetes, GI infection, and inflammatory bowel disease should also exercise caution[21].

Allicin has been observed to substantially inhibit the CYP2E1 isozyme, reducing its activity by up to 39%[22]. Consequently, elevations in drugs metabolised by 2E1 may be expected. These include paracetamol and alcohol.

As an inducer of the CYP3A4 isozyme[23], an increased consumption of garlic may stimulate the metabolism of certain drugs including birth control.

Adverse Effects

Gastrointestinal upset is the most common complaint with supplemental garlic consumption[24]. This entails heartburn, intestinal gas and bloating, nausea and vomiting, and diarrhoea. A tolerance may develop to these side effects over time. Certain extracts may be associated with less gastrointestinal upset.




Reishi Mushroom

ganoderma lucidum

The Reishi mushroom is a fungal remedy which has been used in traditional Chinese medicine. Its major studied properties include antioxidant, antineoplastic, and immunomodulatory activity[25].

Its pharmacologic effects derive from many bioactive molecules, which include various polysaccharides and triterpenes, among others. Polysaccharides seem to be involved in modulating the immune system[26], which entails stimulating the proliferation and differentiation of T-lymphocytes & NK cells, for example, when the immune system is weakened, and attenuating TNFα and some interleukin activity when the immune system is over-functioning (e.g. auto-immune disease).

Warnings

This supplement should be avoided in individuals with an autoimmune disease (e.g. multiple sclerosis) or immunosuppression therapy (e.g. for transplant recipients)[27]. Ganoderma‘s immunomodulating effects may trigger disease flares or organ rejection.

Use within 2 weeks of surgery is also not recommended as with garlic extracts[28]. Some constituents in Ganoderma inhibit platelet aggregation, producing a clinically significant effect at doses over 3 grams per day. Thus, individuals taking Ganoderma may be at a higher risk of bleeding.

Ganoderma may interact with certain medications for diabetes and blood pressure by contributing to their effects[29]. In individuals receiving antidiabetics such as insulin or glipizide, supplementing Ganoderma may increase the risk of hypoglycaemia, or dangerously low blood sugar which may lead to a seizure. Individuals taking medications for blood pressure, such as lisinopril, may be at a higher risk of hypotension, or very low blood pressure which may lead to shock.

Adverse Effects

The most frequently reported side effects with Ganoderma supplementation are bleeding[30], rash, dizziness, and headache.




Lion’s Mane Mushroom

lion's maneHericium is another medicinal fungus used in traditional Chinese therapeutics as well as in cuisine. It is named for its characteristic spines. H. erinaceus has been observed to produce various beneficial effects when consumed, ranging from enhancement of metabolic processes (such as fat metabolism)[31] to neurogenesis[32], to name a few.

Hericium erinaceus preparations contain molecules which may stimulate or suppress elements of the immune system[33]. Polysaccharides have been observed to promote macrophage activity while some other components of Lion’s mane preparations have been shown to inhibit chemotaxis[34].

Lion’s mane is available as powdered mushroom or the more potent powdered extract (in different strengths, e.g. 10:1 extract with 30% polysaccharide content). The typical dosage is as follows: 1 g of the purified extract by mouth three times a day with food[35]. As with all of these supplements, a lower starting dosage with a scheduled titration may be considered.

Adverse Effects

Hericium may cause itching. If this occurs without signs and symptoms of an allergic reaction such as hives, it is most likely due to nerve sensitivity in the setting of elevated Nerve Growth Factor (NGF)[36]. The long-term safety of Hericium is uncharacterised.




Vitamin C

vitamin c

This water-soluble vitamin has been traditionally recommended as an immune system booster specifically with regard to the common cold[37]. However, the data are highly conflictive as to whether supplementing vitamin C actually helps[38].

Vitamin C is purported to support the immune system through its function as an antioxidant, protecting host cells from oxidative stress caused by pathogens.

Stronger evidence supports the use of vitamin C to marginally reduce the duration of cold symptoms by approximately 1 to 1.5 days. A 2013 Cochrane meta-analysis found in 24 trials that studied the general population, supplementing vitamin C did not significantly reduce the risk of developing a cold (RR 0.97, 95% CI 0.94–1.00)[39]. The same meta-analysis found that regular vitamin C supplementation could modestly reduce the duration and the severity of cold symptoms. Adults experienced an 8% reduction (3–12%) and children a 14% reduction (7-21%).

Formulations & Dosage

While vitamin C is better absorbed at lower doses, it appears that higher doses are required to achieve benefit. A dosage of 1–3 g by mouth daily is recommended starting at the onset of symptoms & continued up to 3-5 days or as long as symptoms persist[40].

Labdoor has published rankings for the best vitamin C formulations.

Warnings

Individuals with G6PD deficiency should exercise caution with higher doses of vitamin C, as there is a risk of precipitating haemolytic anaemia[41].

Vitamin C is generally well-tolerated[42]. At high doses, however, adverse effects may present themselves. These include gastrointestinal upset marked by nausea, vomiting and diarrhoea and flushing of the skin.




Colostrum

colostrumColostrum is a rich pre-milk fluid derived from cows during the first 2–4 days after birth. This substance contains immune factors, amino acids, minerals, and other nutrients which promote the growth of the offspring[43]. Nutrients from colostrum support general metabolic functioning while other compounds may have intrinsic antimicrobial activity. Colostrum in particular provides a substantial amount of secretory immunoglobulin A (IgA), which is an antibody involved in the humoral immune response[44].

It is debatable whether adults would benefit from consumption of colostrum as much as newborns[45]. Newborns have a relatively undeveloped gastrointestinal system which does not degrade food intake to the extent that a fully developed gastrointestinal system would. An adult’s stomach would more likely break down many of the helpful constituents present in colostrum. Colostrum has been used to prevent some gastrointestinal infections in children, such as infectious diarrhoea & gastroenteritis. It may also be effective in preventing these infections in immunocompromised patients, such as individuals with AIDS. However, the efficacy of colostrum as an immune system booster in the healthy adult population has not been substantiated.

Warnings

Because colostrum is a dairy product, it is not recommended for individuals with lactose intolerance or dairy allergy.

Heat-denatured bovine immunoglobulin present in colostrum may contribute to atherosclerotic processes[46]. Patients with high cholesterol should discuss with their doctor or pharmacist before use.

Colostrum is generally well-tolerated. The most common side effects experienced with colostrum are gastrointestinal in nature, such as nausea, vomiting, diarrhea, intestinal gas, and bloating.




Conclusion

There are many different ways to augment your immune system, reducing your risk of becoming sick & attenuating symptoms of being sick. Before starting any substance, research how it works, how to take it (e.g. when to start, how much, when to stop, etc.), and any warnings (e.g. colostrum should not be tried in individuals with a dairy allergy). Stay safe!

References   [ + ]

1. Owen JA, Punt J, Stranford SA. Immunology. 7th ed. New York: W.H. Freeman & Company; c2013. Chapter 1, Overview of the Immune System.
2. Eby GA, Davis DR, Halcomb WW. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrobial Agents & Chemotherapy 1984;25:20-4.
3, 10, 11, 14. Zinc. Natural Medicines®. Therapeutic Research Center, Somerville, Massachusetts, USA. [updated 17 Jun 2015].
4. Sheikh A, Shamsuzzaman S, Ahmad SM, Nasrin D, Nahar S, Alam MM, Al Tarique A, Begum YA, Qadri SS, Chowdhury MI, Saha A, Larson CP, & Qadri F. Zinc influences innate immune responses in children with enterotoxigenic Escherichia coli-induced diarrhea. J Nutr 2010;140(5):1049-1056.
5. Licastro F, Chiricolo M, Mocchegiani E, et al. Oral zinc supplementation in Down’s syndrome subjects decreased infections & normalized some humoral & cellular immune parameters. J Intellect Disabil Res 1994;38:149-62.
6. Stabile A, Pesaresi MA, Stabile, AM, Pastore M, Sopo SM, Ricci R, Celestini E, & Segni G. Immunodeficiency & plasma zinc levels in children with Down’s syndrome: a long-term follow-up of oral zinc supplementation. Clin Immunol.Immunopathol. 1991;58(2):207-216.
7. Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD001364. DOI: 10.1002/14651858.CD001364.pub4.
8. DiSilvestro RA. Handbook of Minerals as Nutritional Supplements. CRC Press: Boca Raton, Florida; 2004.
9. Eby GA. Zinc lozenges as cure for the common cold– a review and hypothesis. Med Hypotheses. 2010 Mar;74(3):482-92.
12, 13. Micromedex® 1.0 (Healthcare Series), (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com/
15. Age-Related Eye Disease Study Research Group. The effect of five-year zinc supplementation on serum zinc, serum cholesterol and hematocrit in persons randomly assigned to treatment group in the age-related eye disease study: AREDS Report No. 7. J Nutr. 2002 Apr;132(4):697-702.
16, 20, 21, 24. Garlic. Natural Medicines®. Therapeutic Research Center, Somerville, Massachusetts, USA. [updated 14 Feb 2015].
17. World Health Organisation. Monographs on Selected Medicinal Plants, Volume I. Geneva: WHO; 1999.
18. Kasuga S, Uda N, Kyo E, Ushijima M, Morihara N, & Itakura Y. Pharmacologic activities of aged garlic extract in comparison with other garlic preparations. J Nutr 2001;131(3s):1080S-1084S.
19. Song K & Milner JA. The influence of heating on the anticancer properties of garlic. J Nutr 2001;131(3s):1054S-1057S.
22. Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-87.
23. Piscitelli SC, Burstein AH, Welden N, et al. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002;34:234-8.
25, 27, 28. Reishi Mushroom. Natural Medicines®. Therapeutic Research Center, Somerville, Massachusetts, USA. [updated 16 Feb 2015].
26. Xu Z, Chen X, Zhong Z, Chen L, & Wang Y. Ganoderma lucidum polysaccharides: immunomodulation & potential anti-tumor activities. Am.J.Chin Med. 2011;39(1):15-27.
29. Gao Y, Lan J, Dai X, Ye J, & Zhou S. A Phase I/II Study of Ling Zhi Mushroom.
30. Tao J & Feng KY. Experimental & clinical studies on inhibitory effect of ganoderma lucidum on platelet aggregation. J Tongji Med Univ 1990;10:240-3.
31. Hiwatashi K, Kosaka Y, Suzuki N, Hata K, Mukaiyama T, Sakamoto K, et al. Yamabushitake mushroom (Hericium erinaceus) improved lipid metabolism in mice fed a high-fat diet. Biosci Biotechnol Biochem. 2010;74(7):1447-51.
32. Wong KH, Naidu M, David RP, Bakar R, Sabaratnam V. Neuroregenerative potential of lion’s mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (higher Basidiomycetes), in the treatment of peripheral nerve injury (review). Int J Med Mushrooms. 2012;14(5):427-46.
33. Kim YO, Lee SW, Oh CH, Rhee YH. Hericium erinaceus suppresses LPS-induced pro-inflammation gene activation in RAW264.7 macrophages. Immunopharmacol Immunotoxicol. 2012 Jun;34(3):504-12.
34. Abdulla MA, Fard AA, Sabaratnam V, Wong KH, Kuppusamy UR, Abdullah N, et al. Potential activity of aqueous extract of culinary-medicinal Lion’s Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) in accelerating wound healing in rats. Int J Med Mushrooms. 2011;13(1):33-9.
35. Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res. 2009 Mar;23(3):367-72.
36. Tanaka A, Matsuda H. Expression of nerve growth factor in itchy skins of atopic NC/NgaTnd mice. J Vet Med Sci. 2005 Sep;67(9):915-9.
37, 40, 41, 42. Vitamin C. Natural Medicines®. Therapeutic Research Center, Somerville, Massachusetts, USA. [updated 17 Mar 2015].
38, 39. Hemilä H, Chalker E. Vitamin C for preventing & treating the common cold. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No.: CD000980. DOI: 10.1002/14651858.CD000980.pub4.
43. Thapa, BR. Health factors in colostrum. Indian J Pediatr 2005;72(7):579-581.
44. He F, Tuomola E, Arvilommi H, Salminen S. Modulation of human humoral immune response through orally administered bovine colostrum. FEMS Immunol Med Microbiol. 2001 Aug;31(2):93-6.
45. Bovine Colostrum. Natural Medicines®. Therapeutic Research Center, Somerville, Massachusetts, USA. [updated 14 Feb 2015].
46. Annand, JC. Denatured bovine immunoglobulin pathogenic in atherosclerosis. Atherosclerosis 1986;59(3):347-351.
Categories
Health

Is Berberine the New Resveratrol?

There are very few supplements that have a list of potential benefits as impressive as berberine. Despite the fact that berberine is not all that well known compared to many other supplements, it is extremely well researched. While not all of these benefits are guaranteed to occur for every single user, berberine has been found to

  1. Reduce inflammation
  2. Improve gastrointestinal health
  3. Reduce glucose production in the liver
  4. Improve markers of insulin resistance
  5. Lower cholesterol
  6. Lower oxidative stress
  7. Help in losing body fat
  8. Slow down aging
  9. Suppress chemical-induced carcinogenesis, clastogenesis, tumor promotion and tumor invasion
  10. Exert antiarrhythmic effects
  11. Exert anti-microbial activity against a wide range of microorganisms.
  12. Exert minor antidepressant effects, as well as work in a synergistic fashion with existing antidepressants

While this list of touted benefits is certainly impressive, berberine also carries with it a number medication interactions, which must be noted with caution (more on this later).

What is Berberine?

goldenseal
Goldenseal

Berberine is an isoquinoline alkaloid and ammonium salt of a bright yellow color that is found in and extracted from a variety of plants from the genus berberis, as well as Coptis chinensisPhellodendron amurense, and Hydrastis canadensis (Goldenseal) and many others. These plants have a history of being used in both traditional Chinese Medicine and Indian Ayurveda as an anti-microbial agent. Berberine appears to be effective in fighting bacteria, fungi, and protozoa. [1] However, these traditional uses of berberine barely scratch the surface of its full capability.

When berberine is ingested orally, it has a relatively low bioavailability of 5% or less. [2] Berberine increases the action of P-Glycoprotein, a substance which actually makes berberine more difficult for the intestines to absorb. Because of this, taking a P-Glycoprotein inhibitor (such as Milk Thistle) can possibly make smaller doses of berberine more effective.[3] Another option is to take Berberine with Coconut oil that contains a fatty acid known as Sodium Caprate which significantly increases the absorption and the efficacy of Berberine.[4][5]

AMPK Modulation

One of berberine’s main mechanisms of action is its ability to activate an enzyme called Adenosine Monophosphate Kinase (AMPK). AMPK is crucial for maintaining energy homeostasis in cells. It is responsible for regulating glucose and other nutrients by sensing their concentrations within cells. [6] The activation of AMPK caused by berberine has multiple different effects. First, the AMPK activation causes an increased uptake of glucose into adipocytes (fat cells). This is one of the major methods through which berberine reduces glucose levels in the blood.[7] In fact, berberine’s antidiabetic effect is so effective that it is regarded as one of the few supplements to be as strong as a pharmaceutical drug. When taken correctly, berberine can be as effective (or even more effective[8] as the popular type II diabetes drug metformin.[9]

Molecular structure of BerberineBerberine also appears to have various positive effects on the heart and the cardiovascular system as a whole. Activated AMPK located in liver cells causes an inhibition of cholesterol and triglyceride synthesis.[10] This change is also linked to a lowering of low-density lipoproteins (“bad” cholesterol) and raising of high-density lipoproteins (“good” cholesterol). Additionally, berberine can lower the levels of LDL by stimulating the synthesis of LDL receptors, which are responsible for removing LDL from the blood.[11] The activation of AMPK induced by berberine also appears to inhibit the synthesis of lipids and lower triglyceride levels, which is useful for individuals who are attempting to lose weight.[12]

In one study, reperfusion (oxidative stress) was induced in rats who had been pre-treated with berberine. The rats treated with berberine displayed significantly less heart damage than those who had not been treated.[13] One study conducted on 24 overweight or obese subjects concluded that berberine was able to reduce blood pressure significantly more than placebo. [14] These effects of berberine—the inhibition of LDL cholesterol and triglyceride synthesis, increase in HDL cholesterol, decrease in lipid production, protection from oxidative stress, and the decrease in blood pressure—all work together to contribute to berberine’s overall positive effect on heart health and weight loss. But that’s not all…

Anti-aging & Anti-cancer

There is some early research evidence that seems to suggest berberine’s efficacy as telomerase inhibitor.[15] Telomerase is a protein that is intricately linked with cell proliferation and the life cycle of cells. Telomeres (the region that telomerase acts upon) are a portion of DNA sequences located at the ends of chromosomes that keep them from deteriorating.

Essentially, the inhibition of telomerase by berberine has potential applications in the area of life extension & longevity as well as a chemopreventive supplement or in conjunction with existing cancer treatments to increase their efficacy.[16]

fight cancerBesides telomerase inhibition, berberine has also been found to suppress the growth of a wide variety of tumor cells[17][18], including breast cancer,[19] leukemia[20], melanoma,[21] epidermoid carcinoma, hepatoma[22], pancreatic cancer[23], oral carcinoma, tongue carcinoma[24], glioblastoma, neuroblastoma[25], prostate[26][27][28] and gastric carcinoma.

Mental Health

Berberine also exhibits minor to moderate antidepressant effects. One study conducted on mice discovered that berberine administration reduced the immobility time of mice in a swim test, which is indicative of antidepressant effects. The same study also concluded that berberine caused significant increases in the levels of dopamine, serotonin, and norepinephrine in the whole brain. It was also discovered that berberine works synergistically with certain antidepressant medications, such as fluoxetine, imipramine, tranylcypromine, and venlafaxine.[29]

New studies suggest berberine may have a potential for inhibition and prevention of Alzheimer’s disease through inhibition of β-amyloids pathways and cholinesterase[30] and through antioxidant capacities. Berberine derivatives are currently being developed as potent acetylcholinesterase (AChE) inhibitors.[31]

As a PCOS treatment

In a 2012 human study[32], 89 Chinese women of reproductive age who met the diagnostic criteria for polycystic ovarian syndrome (PCOS) and insulin resistance, were recruited and prescribed the anti-androgen compound cyproterone acetate (2.0 mg/day) in a combined oral contraceptive pill with 35 mcg ethinyl estradiol, taken in a cyclic fashion. They also received advice from a nutritionist to limit dietary fat and carbohydrates without restricting calories.

They were then assigned to one out of three treatment groups:

  1. Berberine hydrochloride, 500 mg 3 times/day (n=31)
  2. Metformin, 500 mg 2 times/day for the first week, then 3 times/day for the remainder of the study (n=30)
  3. Placebo tablet 2 times/day (n=28)

Results of the study were:[33]

  • After 3 months, all the treatment groups showed a significant reduction in body weight and BMI.
  • Waist circumference and waist-to-hip ratio were reduced in all 3 groups. However, the berberine group showed a significantly greater reduction in these measures.
  • All 3 treatment groups showed a significant reduction in fasting insulin. However, in the placebo group, fasting plasma glucose and fasting glucose/insulin ratio remained unchanged.
  • Fasting plasma glucose decreased and fasting glucose/insulin ratio increased in the berberine and metformin groups. There was no significant difference between them.
  • The berberine and metformin groups showed comparable changes in total testosterone and free androgen index, which were significantly greater than placebo. However, sex hormone–binding globulin increased significantly in the berberine group when compared with both metformin and placebo.
  • All 3 groups had reductions in total cholesterol and triglycerides. The berberine group had a significantly greater decrease in triglycerides, total cholesterol, and LDL (“bad” cholesterol”), and a significantly greater increase in HDL (“good” cholesterol) when compared to metformin.
  • Adverse effects were minimal and fewer compared to metformin. Nine subjects who received metformin complained of transient abdominal discomfort including nausea, vomiting, mild diarrhea, and flatulence, while 3 who received berberine complained of a bitter taste in the mouth.

As a result of this study, the researchers conclude that berberine may prove a viable alternative to metformin in optimizing the health outcomes of women with PCOS.
Another study[34] on 102 anovulatory Chinese women was published in 2015 found that administration of berberine alone may improve the menstrual pattern and ovulation rate in anovulatory Chinese women with polycystic ovary syndrome, as well as decrease sex hormone binding globulin, insulin resistance, total cholesterol, triglycerides and low-density lipoprotein cholesterol in normal weight polycystic ovary syndrome women.

Side Effects & Interactions

Berberine is absorbed slowly by the intestine, meaning that high doses can cause diarrhea and cramping. For this reason, berberine is typically taken in various smaller doses throughout the day.

In terms of interactions, the most noteworthy is the potential interaction with macrolide antibiotics like azithromycin (Zithromax) and clarithromycin (Biaxin). The interaction between the two has the possibility of causing cardiotoxicity. Berberine also inhibits enzymes CYP2D6 and CYP3A4 which has the potential to affect how many other drugs are metabolized by the body.[35] For this reason, it is very important to discuss berberine supplementation with a healthcare professional to ensure no dangerous interactions will take place.

Goldenseal vs Berberine Hcl

berberine supplement
Berberine hydrochloride powder

The two most common ways to supplement Berberine are to take either Berberine hydrochloride (hcl) or Goldenseal root powder. This is extremely important and I’ll explain why.

Goldenseal, – which contains a number of other compounds besides berberine – has been shown to cause DNA damage in prokaryotic and eukaryotic organisms[36] as well as promote liver cancer in rats.[37]

Therefore, I strongly advise against using goldenseal root and to take Berberine Hcl instead, the same way it was used in the PCOS studies. If you’re taking goldenseal supplements, stop taking them as soon as possible!

Conclusion

Berberine is certainly unique among supplements in the fact that it is equally as effective as some prescription medications. It also boasts a myriad of benefits that impact a variety of systems throughout the body. This article has only scratched the surface of the researched benefits of berberine. A collation of the large body of evidence concerning berberine can be found here for anyone who wants to learn more about this fascinating supplement. While there are some potential side effects and medication interactions, berberine is still well worth checking out. Berberine stands as a hidden gem among supplements – one that has the potential to greatly improve one’s quality of life.

Berberine Hcl can be bought relatively cheap at PowderCity and other supplement and vitamins shop.

References   [ + ]

1. Berberine at Examine.com
2. Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats.
3. Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp.
4. Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis (2012)
5. Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine (2010)
6. Effect of AMPK activation on muscle glucose metabolism in conscious rats.
7. Berberine inhibits PTP1B activity and mimics insulin action.
8. Berberine Compared to Metformin in Women with PCOS | Natural Medicine Journal
9, 35. Berberine at Examine.com
10. Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine.
11. Berberine inhibits dyslipidemia in C57BL/6 mice with lipopolysaccharide induced inflammation.
12. Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine
13. Berberine attenuates ischemia-reperfusion injury via regulation of adenosine-5′-monophosphate kinase activity in both non-ischemic and ischemic areas of the rat heart.
14. Effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion.
15. Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer.
16. Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer.
17. A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs (2009)
18. Berberine and Coptidis Rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations (2009)
19. The alkaloid Berberine inhibits the growth of Anoikis-resistant MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell cycle arrest (2009)
20. Down-regulation of cyclin B1 and up-regulation of Wee1 by berberine promotes entry of leukemia cells into the G2/M-phase of the cell cycle (2006)
21. Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line (2008)
22. Coptis chinensis inhibits hepatocellular carcinoma cell growth through nonsteroidal anti-inflammatory drug-activated gene activation (2009)
23. Berberine Inhibits Cell Growth and Mediates Caspase-Independent Cell Death in Human Pancreatic Cancer Cells (2010)
24. Berberine induced apoptosis via promoting the expression of caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G in SCC-4 human tongue squamous carcinoma cancer cells (2009)
25. Berberine inhibits human neuroblastoma cell growth through induction of p53-dependent apoptosis (2008)
26. Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells (2006)
27. Butanol fraction containing berberine or related compound from nexrutine inhibits NFκB signaling and induces apoptosis in prostate cancer cells (2009)
28. Berberine inhibits p53-dependent cell growth through induction of apoptosis of prostate cancer cells (2009)
29. On the mechanism of antidepressant-like action of berberine chloride.
30. Conformation-activity studies on the interaction of berberine with acetylcholinesterase: Physical chemistry approach (2009)
31. Synthesis, biological evaluation, and molecular modeling of berberine derivatives as potent acetylcholinesterase inhibitors (2009)
32, 33. Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial
34. A Single Arm Pilot Study of Effects of Berberine on the Menstrual Pattern, Ovulation Rate, Hormonal and Metabolic Profiles in Anovulatory Chinese Women with Polycystic Ovary Syndrome
36. Genotoxicity of the isoquinoline alkaloid berberine in prokaryotic and eukaryotic organisms
37. Toxicology and carcinogenesis studies of goldenseal root powder (Hydrastis Canadensis) in F344/N rats and B6C3F1 mice