Bitter Melon and Diabetes

Diabetes is a condition that affects blood sugar levels and can lead to health issues if not properly managed. Could eating bitter melon be healthful for those looking to manage diabetes?

The bodies of people with diabetes do not produce enough insulin or are not able to use insulin effectively, which leads to there being too much glucose in the blood. Insulin is required so that cells can use it for energy.

A healthful diet and exercise are important for people with diabetes to help them manage their condition. Certain foods can cause blood sugar levels to spike, which is problematic.

In this article, we explore whether the bitter melon is healthful for people looking to manage diabetes. As part of this, we analyze the impact bitter melon may have on blood sugar.

Treating diabetes

bitter melons on a wooden table
Some people with diabetes look to natural treatments, such as bitter melon, to help manage their symptoms.

In type 1 diabetes, high blood sugar is the result of the body not producing enough insulin.

Type 2 diabetes, however, occurs when the body does not respond correctly to insulin. Type 2 diabetes is the most common form of diabetes, and people of any age can develop it.

Many people with diabetes manage their condition well and do not experience further health problems. A range of medications and lifestyle changes can help people with diabetes live healthy lives.

However, drug therapies may have some side effects. As such, some people look to try natural treatments that are free of side effects. To make an informed decision about these, it helps to understand the science behind these options.

One such natural treatment method is better melon. Although further research is needed to draw reliable conclusions, some research suggests bitter melon may normalize blood glucose levels.

What is bitter melon?

Bitter melon has many different names, depending on where you are in the world. People all around the world have used it for both food and medicine for centuries.

Rich in vitamins and minerals, bitter melon grows on a vine of the Momordica charantia plant and is the most bitter of all fruits and vegetables.

Bitter melon grows in tropical and subtropical environments and thrives in:

  • South America
  • Asia
  • the Caribbean
  • some parts of Africa

An alternative remedy for centuries, people are said to have used it to manage:

  • colic
  • fevers
  • burns
  • coughs
  • skin conditions
  • childbirth

In parts of Asia and Africa, it has been used to manage symptoms of chicken pox and measles. And researchers from St. Louis University have even found evidence that bitter melon can hinder the growth of breast cancer cells.

How does bitter melon affect people with diabetes?

It is believed that bitter melon could have properties which lower blood sugar levels.

A number of clinical studies have examined the effect bitter melon has on diabetes to see whether it could be an effective treatment for normalizing blood glucose.

Effect on blood sugar levels

Researchers believe bitter melon contains substances that cause decreases in blood glucose and appetite suppression. In this way, it behaves similarly to insulin.

One study published in the Journal of Ethnopharmacology found that 2,000 mg daily of bitter melon lowers blood glucose levels considerably in people with type 2 diabetes. The effect was less than taking a 1,000 mg dose of metformin, which is a medicine often prescribed to control blood sugar levels.

Effect on glucose intolerance

Another study from 2008, suggests bitter melon improves glucose intolerance and suppresses blood glucose levels after meal consumption in animal studies.

However, other studies suggest any improvement is insignificant or inclusive.

Effect on hemoglobin A1c levels

Another study aimed to determine whether people with diabetes who took bitter melon supplements could decrease their hemoglobin A1c levels.

A1c levels are the average blood sugar levels over a 2-3 month period. The study looked to see if bitter melon could reduce A1c levels by at least 1 percent over this three-month period.

Two groups of people took part in the study:

  • people recently diagnosed with type 2 diabetes
  • those with poor glucose control, who had A1c levels from 7 to 9 percent

The participants were advised to take two capsules of bitter melon three times daily.

The results of the study, reported in the Journal of Clinical Epidemiology, uncovered a less than 0.25 percent decrease in A1c levels in the study group.

The placebo group showed no change. The authors noted that the study size was too small but showed potential for larger studies.

Compared to no treatment

A 2014 report from Nutrition and Diabetes, looked at four studies that compared treatment using bitter melon supplements to no diabetic treatment at all.

The authors of the study found no evidence bitter melon had any significant effects on A1c levels or fasting plasma glucose levels.

They further concluded most of the research to date is inclusive regarding glycemic outcomes. They believed larger sample sizes could better determine bitter melon’s effectiveness as a supplemental treatment for diabetes.

Further research

A 2016 report published in Current Pharmacology Reports similarly looked at several studies related to bitter melon including its effects on diabetes.

The authors did find merit in the theories that bitter melon may have hypoglycemia (low blood glucose) properties.

They also found it may help to reduce the adverse effects of diabetes but felt further study was warranted to come to any real conclusions.

Using bitter melon as a supplemental diabetes treatment

drinking a green juice after exercise
Bitter melon is also available as a juice.

Bitter melon is available in many forms, including as:

  • a fruit
  • a powder
  • an herbal supplement
  • juice

The fruit is available at most Asian grocery stores. Powders, Supplements, and juices are available at health food stores and sold by online retailers.

How much to consume

Anyone considering taking bitter melon alongside their diabetes treatment should consume no more than:

  • 50-100 milliliters daily (or about 2 to 3 ounces spread throughout the day)
  • one small bitter melon per day

Supplements should be taken according to the instructions on the packaging. People should check with their doctors to see if it is safe to include supplements to their treatment plan. This is because supplements may counteract the effects of diabetes medications.

Risks of consuming bitter melon

Excessive consumption of bitter melon may cause stomach troubles, including diarrhea. Another potential adverse effect is extremely low blood sugar.

Children should not take bitter melon as it has been known to cause vomiting and diarrhea. Pregnant women should not consume bitter melon in any form because it has been associated with bleeding, contractions, and miscarriage.

Conclusion

Bitter melon is generally safe for most adults. However, as reported by the International Journal of Environmental Research and Public Health, possible side effects caused by long-term use have not been studied.

Whilst there may be some benefits, no double-blind, placebo-controlled study (the gold standard of studies) has proven effectiveness or safety in all people with diabetes. People with diabetes should use bitter melon with caution, due to the associated hypoglycemia risks.

People with diabetes wanting to include bitter melon in their treatment plan should consult with their doctors. They should monitor their blood glucose levels closely because bitter melon may interact with diabetes medications that might reduce blood sugar to dangerous levels.

With more research, however, bitter melon may become a standard treatment for diabetes management.

Can Turmeric Help Manage Diabetes?

Turmeric has been used for centuries in both food and medicine. The spice is believed to have many potential benefits for the human body. But could turmeric be a new tool to help manage diabetes?

Turmeric is the common name for the root Curcuma longa. It is a bright yellow-orange spice that is a staple in traditional food dishes from many Asian countries.

In this article, we explore the role of turmeric in alternative and Western medicine. We go on to analyze the potential benefits of the spice for diabetes management.

Turmeric and medicine

turmeric
Turmeric and its compounds are being studied for conditions such as cancer, inflammation, and psoriasis.

Turmeric plays an important role in medical practices, such as Ayurveda and Traditional Chinese Medicine (TCM).

Medical science is interested in the herb, as well, due to the high levels of friendly compounds it contains. Of particular interest is a class of compounds called curcuminoids.

One curcuminoid found in turmeric is curcumin. This name is sometimes loosely used to describe all of the curcuminoids in turmeric.

Turmeric and curcumin are being studied for a number of human conditions such as:

  • irritable bowel syndrome
  • inflammatory bowel disease
  • cancer
  • arthritis
  • uveitis
  • peptic ulcers
  • inflammation
  • h. pylori infections
  • vitiligo
  • psoriasis
  • Alzheimer’s disease

Turmeric is also often added to the diet to help reduce inflammation and oxidative stress.

Can turmeric help people with diabetes?

Including turmeric in the diet seems to promote general wellbeing. There is also evidence that indicates turmeric may be especially beneficial for people with diabetes.

It is believed that curcumin is the source of many of the medical benefits of turmeric. The focus of most research has been on curcumin itself, rather than the whole turmeric.

A review in the journal Evidence-Based Complementary and Alternative Medicine compiled more than 13 years of research on the connection between diabetes and curcumin. The result suggests curcumin can help people with diabetes in different ways, as described here:

Curcumin may help control blood sugar

Curcumin may help people with diabetes control their blood sugar levels.

Tests using animal models indicated that curcumin could have a positive effect on high blood sugar. Many tests were also able to improve the levels of insulin sensitivity in test subjects. Other studies found that curcumin had little effect on blood sugar.

Thus, taking turmeric or curcumin orally may help reduce blood sugar levels to more controllable levels in some people, though more research on humans is necessary.

Curcumin may help prevent diabetes

curcumin capsule turmeric
Studies suggest that people with prediabetes may not develop full diabetes when given curcumin in capsules.

Researchers also noted that many of the studies done over the years showed turmeric might also protect against developing diabetes. One study posted to Diabetes Care found that people with prediabetes who were given curcumin for a period of 9 months were less likely to develop the full-blown condition.

The study also noted that the curcumin appeared to improve the function of the beta cells that make insulin in the pancreas. Accordingly, including turmeric or curcumin in the diet may be beneficial for people who want to reduce their chance of developing diabetes.

Curcumin may reduce diabetes-related complications

Compounds like curcumin may also help with a few diabetes-related complications.

People with diabetes often have liver disorders, such as fatty liver disease. Researchers gave test subjects curcumin over a long period of time. As a result, these people appeared to have fewer symptoms of liver disorders.

Curcumin may also help:

  • prevent nerve damage caused by diabetes
  • prevent diabetic cataracts, according to results of animal tests
  • fight cognitive problems, due to antioxidant and anti-inflammatory properties
  • fight kidney disease, by reducing important markers

The compound curcumin was reported to be active against diabetic vascular disease, and it seems to speed wound-healing. There is also evidence that suggests long-term curcumin intake can improve aspects of digestion.

Curcumin may adjust immune response in type 1 diabetes

An article posted to Clinical and Experimental Immunology also noted that curcumin may adjust how the over-active immune system works in people with type 1 diabetes.

Researchers found that curcumin lowers the T cell response of the body. This is the immune response that destroys the pancreatic beta cells that make insulin.

This means that curcumin may help empower the immune system. Similarly, it may boost the immunomodulatory medicines prescribed to manage type 1 diabetes.

Risks, considerations, and side effects

Before taking any new supplements, a healthcare professional should be consulted.

Turmeric is considered safe and can be included in the diet regularly. However, there is the potential for side effects when turmeric or curcumin are taken in large doses. Some people experience symptoms of indigestion, nausea, or diarrhea if they take too much of either.

People with certain conditions may need to avoid turmeric altogether, as it may make these worse. Conditions that might be affected include:

  • gallbladder disease
  • kidney stones
  • anemia

Taking too much curcumin or turmeric for a long period of time may also contribute to liver problems.

Similarly, the spice may increase the effects of other blood sugar medications, potentially leading to hypoglycemia or low blood sugar. The best course of action is for people to work with a knowledgeable doctor or healthcare practitioner before using supplements like curcumin for any of their symptoms.

Turmeric and diabetes management

If people with diabetes add turmeric to their diets, it should be used as a supplement to a comprehensive diabetes management plan.

Many people with diabetes respond well to:

  • eating a healthful diet
  • exercising regularly
  • managing their stress levels

Doctors will often work directly with a person to create an individualized health plan that addresses their specific symptoms.

A good diet plan for people with diabetes usually begins with a move away from processed foods. People should aim for a diet rich in natural, unprocessed meals instead. Eating a wide variety of vegetables, fruits, and grains helps to ensure a diet contains as many nutrients as possible.

People with diabetes must watch their carbohydrate intake, particular carbohydrates in processed and refined sugars, as these can cause spikes in the blood sugar. Although natural sugars such as those found in fruit are better options, these also need to be accounted for when managing diabetes.

Fiber-rich foods are also needed, as they slow the rate of sugar absorption in the body. This may help prevent blood sugar spikes during the day.

Including plenty of other healthy spices besides turmeric in the diet may also help some people manage their diabetes symptoms. These include:

  • cinnamon
  • ginger
  • cumin

Criticisms of turmeric and curcumin

Not everyone is convinced curcumin is as good as it seems.

A recent study posted in the Journal of Medicinal Chemistry was critical of the use of curcumin to help prevent or treat anything.

The researchers argued that curcumin is not very bioavailable and that the quality of the herb can vary greatly. This makes it difficult to use or test its compounds in a controlled way. They called for a more careful examination of curcumin in future research.

Outlook on taking turmeric for diabetes

Turmeric is not a medicine in the Western sense of the word. It is not a replacement for any medications a person may be taking. It should also not be used as a substitute for any part of diabetes care.

Both turmeric and curcumin can easily be taken to supplement a diabetes-care regimen. This should be done under the guidance of a doctor, who may ask a person to start out with a low dose to gauge their reaction to it. The dose can be increased, gradually, to avoid any complications or side effects.

Pairing turmeric or curcumin with oils, fats, or black pepper may also increase the effect of their beneficial compounds.

Home Remedies for Bronchitis

Bronchitis is an inflammation or swelling of the lining of the bronchial tubes, otherwise known as the bronchi.

The bronchi are the passages that connect the lungs to the mouth and nose. But what home remedies are best to treat bronchitis?

People with bronchitis experience breathing difficulties caused by a reduced capacity to carry air through the bronchi into the lungs. They also tend to have mucus or phlegm in their airways.

Several treatments, including many home remedies, are available to treat bronchitis and its symptoms. This article looks at how effective these treatments may be so that people with bronchitis can make an informed decision about how to treat it.

Drinking warm liquids

Warm water, tea, and other hot drinks help to thin mucus, making coughing easier.

A 2008 study suggests that hot beverages can provide “immediate and sustained relief from symptoms of a runny nose, cough, sneezing, sore throat, chilliness, and tiredness”.

Ginger tea may also help bronchitis symptoms, as ginger is a natural anti-inflammatory.

Using a humidifier

Keeping the air in the home or workplace moist helps to loosen mucus in the airways and reduce coughing. The National Heart, Lung, and Blood Institute recommend a cool-mist humidifier or steam vaporizer to do this.

A 2014 study indicates that long-term humidification therapy is a cost-effective treatment for people with the chronic obstructive pulmonary disease (COPD) or bronchiectasis. However, researchers cautioned that more investigation was necessary.

COPD is an umbrella term for a number of lung conditions including bronchitis and bronchiectasis, which is a condition where the airways become abnormally wide.

If a person with one of these conditions uses a humidifier, it should be regularly cleaned, according to the manufacturer’s guidelines, to kill bacteria and other pathogens that make symptoms worse.

Wearing a face mask in cold weather

Being hit by sudden cold air can increase a cough. Covering up the mouth and nose before going outside in cold weather can help to reduce coughing and shortness of breath. Cold-air face masks are available, or the mouth can be covered with a scarf or other item of clothing.

Honey

Honey is often used as a natural remedy for a cough, and it is said to have both antiviral and antibacterial properties.

Research into the effectiveness of honey for respiratory tract infections indicates it may be an effective home treatment.

A 2007 study looked at how well dark honey worked for children with bronchitis. While the children who took the honey experienced greater symptom relief than those taking the placebo, the clinical benefit was small. Honey should not be given to children under 1 year.

Pursed-lip breathing techniques

A breathing technique known as pursed-lip breathing may benefit people with bronchitis, as well as those with COPD.

The COPD Foundation advise that this technique helps people breathe easier by:

  • keeping airways open longer
  • slowing down breathing
  • helping the lungs eliminate stale, trapped air
  • improving the exchange of oxygen and carbon dioxide
  • increasing the time that can be spent on certain activities

Pursed-lip breathing involves inhaling through the nose for 2 seconds, before puckering the lips and exhaling slowly through the mouth for 4 to 6 seconds.

Essential oils

Eucalyptus oil
Essential oils such as eucalyptus may help to reduce airway inflammation.

Many people with bronchitis or COPD use essential oils to ease symptoms, particularly inflammation and breathing difficulties.

Some research suggests airway inflammation can be reduced by using myrtol, eucalyptus oil, or orange oil, with myrtol oil showing additional benefits against inflammation.

An animal study also found that oil from the flower Zataria multiflora reduced inflammation in guinea pigs with COPD.

Other essential oils which may help ease the breathing difficulties associated with bronchitis include:

  • basil
  • eucalyptus
  • peppermint
  • rosemary
  • tea tree
  • thyme
  • oregano

Essential oils can be inhaled directly or used in a diffuser. Never take essential oils internally or apply them directly to the skin. To use on the skin, mix them with a carrier oil, such as mineral oil or sweet almond oil. Usually, it is 3-5 drops per 1 ounce of carrier oil.

Ginseng extract

Ginseng is a popular herbal remedy extracted from the fleshy roots of various slow-growing perennial plants.

In some research, ginseng extract was found to reduce the number of bacteria in the lungs of people with chronic bronchitis, who were having an attack of acute bronchitis.

Ginseng also has anti-inflammatory qualities, which may help it quell inflammation in the bronchial tubes.

N-acetylcysteine (NAC)

This supplement is a modified version of the amino acid cysteine. It may help to reduce both the frequency and severity of coughing. NAC may also thin the mucus in the bronchi, allowing it to be eliminated from the body more easily.

An analysis of 13 studies on NAC for chronic bronchitis or COPD suggests that people with chronic bronchitis and an airway obstruction benefit from 1,200 milligrams (mg) per day. Those with bronchitis without an airway obstruction see benefits from a regular dose of 600 mg daily.

Vitamin D

According to the Vitamin D Council, many studies indicate that people who have low levels of the vitamin are more prone to respiratory infections, including COPD.

Other research suggests that those who have high vitamin D levels experience shorter bouts of respiratory infections or milder symptoms.

However, the evidence is mixed when it comes to taking vitamin D to treat respiratory infections. Nonetheless, vitamin D is important for overall health and supplementation is a low-risk approach to bronchitis treatment.

If you choose to use supplements, essential oils, or herbs, be aware that these are not monitored by the U.S. Food and Drug Administration (FDA) for safety, quality, purity, or packaging. Choose to buy from a company you trust.

Types of bronchitis

There are two types of bronchitis known as acute and chronic.

Acute bronchitis, or a chest cold, is a common condition which can develop from a cold or respiratory infection. People tend to recover from acute bronchitis within 10 to 14 days.

Chronic bronchitis is characterized by a constant irritation of the bronchi that lasts 3 months or more, or recurrent episodes of bronchitis for at least 2 years. In 2015, 9 million Americans were diagnosed with chronic bronchitis.

Symptoms of chronic bronchitis may worsen periodically, which indicates acute bronchitis in conjunction with the chronic condition.

Causes of bronchitis

The causes of bronchitis vary depending on the type.

Acute bronchitis is most commonly caused by a virus, particularly those that cause cold and flu. Viruses do not respond to antibiotic treatment, and so antibiotics should not be prescribed to someone who has acute bronchitis caused by a virus.

Smoking is the most common cause of chronic bronchitis, although air pollution or dust can be a factor in some cases.

Risk factors

A very large percentage of people who develop bronchitis have a history of smoking.

Several risk factors are linked with the onset of bronchitis, including:

  • Poor immunity: People with lowered immunity are more vulnerable to bronchitis. Factors which reduce immunity include illness, viral infection, and age. Older adults and young children are at greater risk.
  • Smoking: Cigarette smoke can irritate the lining of the bronchial tubes, which can result in bronchitis. More than 90 percent of people diagnosed with chronic bronchitis have a history of smoking. However, even passive smoke can be a risk factor. A 2012 study found that exposure to passive smoking at work almost doubled the risk of chronic bronchitis, while passive smoking at home increased the risk by 2.5 times.
  • Other irritants: Continued exposure to grains, chemicals, dust, and fabric is known to cause irritation to the delicate lining of the bronchi.
  • Heartburn: The acid that rises due to heartburn causes inflammation in the bronchial tubes.

Symptoms of bronchitis

The most common symptoms of bronchitis are:

  • cough
  • difficulty breathing
  • mucus exhaustion
  • generalized discomfort in the chest
  • low-grade fever
  • chills

People with acute bronchitis may also have had other symptoms consistent with cold or flu that contributed to the development of bronchitis. Examples of such symptoms include:

  • headache
  • runny nose
  • sore throat

Complications

Approximately 1 in 20 cases of bronchitis result in pneumonia. In addition, repeated episodes of bronchitis can indicate COPD.

Preventing Bronchitis

There are several steps to take to reduce the risk of developing acute or chronic bronchitis:

  • Avoid irritants: If contact with lung irritants is unavoidable, take steps to reduce exposure. For example, increase ventilation or wear a mask.
  • Quit smoking: Cutting out tobacco and avoiding exposure to secondhand smoke will help.
  • Improve immunity: Addressing underlying health conditions, eating a balanced diet, working out, reducing stress, and getting enough sleep all help.
  • Limit exposure to bacteria and viruses where possible: Do this by washing hands frequently.
  • Discuss vaccinations with a doctor: These may reduce the risk of bronchitis.

When to see a doctor

It is important to consult a doctor if symptoms of bronchitis endure beyond 3 weeks, are accompanied by a fever, or interfere with sleep.

Seek immediate medical attention if breathing difficulties become severe, or coughing produces blood.

Casperome®, a Frankincense Extract, Controls Minor Symptoms of Ulcerative Colitis in Remission

Ulcerative colitis (UC), an inflammatory bowel disease, is characterized by various symptoms depending on the severity of inflammation and its location. Therapies range from topical therapy with 5-aminosalicylic acid (5-ASA) to treat active proctitis to topical and oral aminosalicylates for mild-to-moderate left-sided colitis and hospitalization and systemic therapy for severe left-sided colitis. The goal of treatment is to induce and maintain a remission phase and prevent disease- and treatment-related complications. For remission maintenance, the first-line therapy is 5-ASA administered orally or rectally. For mild cases of the disease, the benefits of long-term maintenance treatment are less certain. Herbal remedies could help manage mild UC during remission. Oleo-gum-resins from frankincense (Boswellia serrata, Burseraceae) have been used traditionally in India and Africa to treat various inflammatory diseases. The goal of this open-label, observational, registry study was to evaluate the efficacy of Casperome® (Indena SpA; Milan, Italy), a standardized frankincense extract, in patients with minimally symptomatic UC in remission phase.

Casperome is a lecithin-based delivery form of a highly purified standardized extract from the gum resin of frankincense and soy (Glycine max, Fabaceae) lecithin in a 1:1 ratio formulated with Phytosome® (Indena SpA; Milan, Italy) technology, which enhances absorption. It is standardized to contain ≥ 25% of triterpenoid acids.

The study, conducted in Italy, included 43 patients with clinically evaluated and confirmed UC who had been in remission for at least 1 year. Their symptoms were minimal, and they were not using any medications. The patients chose to receive the oral daily Casperome supplementation (n=22) or no supplementation (control group, n=21). The patients in the treatment group consumed one 250-mg Casperome tablet daily for 4 weeks.

At baseline and after 4 weeks, the following parameters were assessed: intestinal pain (ranging from no pain at 1 to continuous, severe pain at 5); bloody diarrhea, as number of episodes weekly; evacuation with blood and mucus, as episodes weekly; bowel movements, as episodes daily; intestinal cramps; suspected rectal involvement; watery stools; malaise; anemia; body weight; white blood cell count; need for specific drugs; and need of medical attention or hospitalization. A fecal immunochemical test was used to detect occult blood in stool samples, which were collected on alternate days. Bowel inflammation was assessed by determining the fecal concentration of calprotectin, an antimicrobial protein released in the intestinal lumen when inflammatory processes are present.

At baseline, all patients were similar in demographics and clinical characteristics. No safety or tolerability issues were observed during the study. Patients who left the study, 5 in the control group and 3 in the treatment group, did not do so for medical problems.

All tested parameters improved significantly after treatment with Casperome. Mild, diffuse intestinal pain and cramps decreased in intensity and frequency in the treatment group compared with the control group and compared with baseline (P<0.05). During the 4 weeks, the episodes of diarrhea, evacuations with blood/mucus, and the number of bowel movements decreased in the treatment group compared with baseline and compared with the control group (P<0.05). The number of patients with suspected rectal involvement remained the same in the control group (13 patients) and decreased from 12 to 4 patients in the treatment group during the 4-week study (P<0.05). Anemia improved significantly in the treatment group from baseline to week 4 and compared with the control group (P<0.05).

In the treatment group, occult blood in the stool decreased during the 4 weeks. The number of patients with calprotectin levels in the stool > 100 μg/g totaled 19 (86.4%) in the treatment group and 18 (85.7%) in the control group at baseline. After 4 weeks, that number decreased significantly to 11 (50%) patients in the treatment group compared with 16 (76.2%) patients in the control group (P<0.05). Significant between-group differences were observed for the need for specific drugs (4 patients in the treatment group and 16 patients in the control group) and for the need for medical attention (9 in the control group and 4 in the treatment group) (P<0.05 for both measures).

Long-term treatment with 5-ASA drugs could have potential adverse effects and is costly. The authors conclude, “Despite all the limitations implicit in any observational analysis, our study demonstrated the Casperome®supplementation efficacy in controlling minor symptoms of UC in remission, and in reducing the use of drugs and medical consultation.” Larger studies are needed to further evaluate these findings.

Three of the authors (E. Milano, F. Franceschi, and S. Togni) are employees of Indena SpA.

Resource:

Pellegrini L, Milano E, Franceschi F, et al. Managing ulcerative colitis in remission phase: usefulness of Casperome®, an innovative lecithin-based delivery system of Boswellia serrata extract. Eur Rev Med Pharmacol Sci. 2016;20(12):2695-2700.

Curcumin Improves Endothelial Function

Damage to the vascular endothelium resulting in endothelial dysfunction has been implicated as an important mechanism in the development of cardiovascular disease (CVD). Curcumin extracts from turmeric (Curcuma longa, Zingiberaceae) rhizome have cardioprotective, antioxidant, and anti-inflammatory properties. Ex vivo, curcumin has been shown to reverse endothelial dysfunction, and one small (n = 32), randomized, controlled trial found curcumin supplementation for 8 weeks was comparable to exercise in improving endothelial function in postmenopausal women. According to the authors, there are no studies evaluating the effect of curcumin supplementation on endothelial function in healthy people. The purpose of this 8-week, randomized, placebo-controlled, double-blind study was to evaluate the effect of high and low doses of a proprietary curcumin supplement on endothelial function in healthy, young adults.

Healthy, nonsmoking men and women (n = 59, aged 19-29 years) participated in this study conducted in Fort Worth, Texas [study dates not reported]. Included subjects had no musculoskeletal, medical, or metabolic contraindications to exercise and did at least 150 min/week of moderate aerobic activity or 75 min/week of vigorous aerobic activity for the 3 months prior to enrollment. Excluded subjects were pregnant or lactating, participated in another clinical trial or consumed the investigational product within the previous 30 days, were regularly treated with anti-inflammatory/analgesic/antioxidant drugs in the previous month, or used any ergogenic aid during the 9 weeks prior to the study.

In this 3-arm trial, subjects received either placebo (corn [Zea mays, Poaceae] starch), 50 mg/day of curcumin (71.5% curcumin, 19.4% desmethoxycurcumin, and 9.1% bisdemethoxycurcumin), or 200 mg/day of curcumin for 8 weeks. The curcumin treatments (CurcuWIN®; OmniActive Health Technologies Ltd.; Mumbai, India) were formulated with a hydrophilic carrier to improve absorption.

Subjects were told to abstain from eating foods that contain curcumin. At baseline and study end, fasting blood was drawn to assess safety, maximal aerobic capacity (treadmill test) was performed to control for the effect of exercise, and flow-mediated dilation (FMD) was assessed with sonography. FMD is a measure of endothelial function. A 1% increase in FMD was considered clinically relevant a priori.

The results of the blood analyses (complete blood count and metabolic panel) were within the normal range, and no adverse events were reported. The maximal aerobic capacity test verified that subjects’ normal exercise routine did not affect endothelial function. The 200 mg/day dose significantly increased FMD (3%) compared to placebo (P < 0.032) and the increase was considered clinically meaningful (˃1%). Inference statistics also indicated that for the 200 mg/day dose, clinical benefit was likely with a benefit-to-harm ratio of 546:1.

The authors conclude that 200 mg/day of CurcuWIN for 8 weeks clinically and significantly increased FMD in healthy, young adults. As FMD is inversely associated with future cardiovascular events in healthy subjects, the authors suggest that curcumin may be “a simple lifestyle strategy for decreasing the risk of cardiovascular diseases in individuals who are apparently healthy.” Further studies are needed to confirm whether the antioxidant and anti-inflammatory actions of curcumin are the mechanisms by which curcumin improves FMD. Limitations of this study include the small sample size, short study duration, and minimal reporting. Markers of inflammation and oxidative stress were not measured, and other CVD risk factors were not assessed or controlled for as variables in the statistical analyses. These results must be confirmed in a larger, longer-duration study using more rigorous methodology. The study was financially supported by OmniActive Health Technologies, the manufacturer of CurcuWIN.

Resource:

Oliver JM, Stoner L, Rowlands DS, et al. Novel form of curcumin improves endothelial function in young, healthy individuals: A double-blind placebo controlled study. J Nutr Metab. 2016;2016:1089653. doi: 10.1155/2016/1089653.

Clinical Efficacy of Australian Eucalyptus and Lemon scent Tea Tree Essential Oils for Head Lice Treatment

  • Australian Eucalyptus (Eucalyptus globulus, Myrtaceae)
  • Lemon-scent Tea Tree (Leptospermum petersonii, Myrtaceae)
  • Head Lice

Head lice infestation, most often seen in children aged 3 to 14 years, causes itching and discomfort, as well as parental anxiety, embarrassment, and school absences. The use of treatments containing neurotoxins has caused safety concerns and has led to resistant lice populations. Alternative treatments have been developed for improved efficacy and concerns about the use of neurotoxins. These authors conducted a multicenter, randomized, parallel-group trial to compare the safety and efficacy of head lice treatments of Australian eucalyptus (Eucalyptus globulus, Myrtaceae) oil and lemon-scent tea tree (Leptospermum petersonii, Myrtaceae) oil (EO/LP) with a neurotoxic mousse containing pyrethrins and piperonyl butoxide (P/PB) in children (trial 1). In trial 2, a single-blind, open trial, the authors studied the efficacy of the EO/LP solution in killing head lice after a single application. Skin irritancy and sensitivity tests were conducted in both adults and children, and the efficacy of EO/LP solution in killing live lice and louse eggs was tested in vitro.

Conducted in Queensland, Australia, the study included male and female schoolchildren up to grade 7 who had live head lice in their hair or on their scalp upon visual inspection and dry-combing with head lice comb.

The EO/LP treatment used was MOOV Head Lice Solution (Ego Pharmaceuticals Pty Ltd; Braeside, Victoria, Australia), which contained 11% per weight eucalyptus oil and 1% per weight lemon-scent tea tree oil. The P/PB treatment was Banlice® Mousse (Pfizer Consumer Healthcare Group; West Ryde, New South Wales, Australia), which contained 1.65 mg/g pyrethrins and 16.5 mg/g piperonyl butoxide.

The EO/LP solution was applied 3 times – on days 0, 7, and 14. Although the P/PB mousse manufacturer recommended only 1 treatment, the mousse was applied twice – on days 0 and 7 – as recommended by the Therapeutic Goods Administration of Australia. The technicians applying the treatments were not blinded because of the physical and smell differences between the treatments; however, the assessment technicians, subjects, and parents did not know which treatment was being used.

The intention-to-treat (ITT) population, which included all randomly assigned subjects before treatment, was used to determine the safety and efficacy. Subjects included in the per-protocol (PP) population were those who completed all treatments of the EO/LP solution or the P/PB mousse. Subjects’ siblings who had lice were treated in the same manner as the subjects and were enrolled in the trial. Siblings with no head lice but with evidence of recent infestation underwent wet-combing. Any adverse effects were recorded at each study visit.

Of the 97 subjects in the ITT population, 76 met the requirements for the PP analysis. Subjects did not meet the PP requirements for the following reasons: 1 did not receive the required dose, 3 used alternative head lice treatments during the trial, 15 failed to comply with sibling control criteria, 1 failed to appear on day 21, and 1 withdrew due to an adverse event. Of the PP population, 40 received the EO/LP solution and 36 received the P/PB mousse.

Analysis of the PP population revealed a significant between-group difference in cure rate at 7 days, with 83% of the EO/LP group cured compared with 36% of the P/PB group (P<0.0001). On day 1, no significant differences were seen in cure rate between the 2 groups. In the ITT subjects, at day 7, 71% in the EO/LP group were cured compared with 33% in the P/PB group (P=0.0002). No significant between-group difference in cure rate was observed on day 1.

Of the 97 subjects who received at least 1 treatment, 21 adverse effects were reported in 13 subjects; the 18 adverse effects reported in the EO/LP group included transient mild to moderate sensations such as itchiness, stinging, or burning lasting no more than 5 minutes and requiring no treatment. The 3 adverse effects in the P/PB group included 1 crawling and 2 stinging sensations.

In trial 2, on day 0, 11 subjects with live lice received treatment with the EO/LP solution. The authors report that after the single EO/LP application, the 1,418 head lice collected were considered dead as they were wet-combed out of the hair. Upon examination 30 minutes after combing, all lice were confirmed dead.

For the skin irritation and sensitivity study, a patch containing the EO/LP solution was applied to the skin of the back for 24 hours every Monday, Wednesday, and Friday for 3 consecutive weeks. Then, 10 to 14 days afterward, 1 challenge or retest dose was applied to a previously unexposed test site and assessed 24 and 48 hours later. Fifty-three of the 56 adult subjects enrolled in this study completed it; 3 withdrew for reasons unrelated to the study protocol. The authors report that no erythema, edema or adverse effects were observed.

For the pediatric testing for skin irritation or sensitivity, 20 children aged 6 months to 4 years were examined on the scalp, face, and neck, and then the EO/LP solution was applied on days 0, 7, and 14. The subjects were evaluated after each application and again 24 hours after the last application. The authors report that no test-related irritation was observed, and no safety-related comments were made by any subjects or their parents.

In testing the in vitro efficacy of the EO/LP solution, the authors observed that no louse eggs hatched for 10 days after a 10-second immersion in the solution. Following immersion in the control (purified water) treatment, 24% of the eggs hatched after 7 days, 76% after 8 days, 92% after 9 days, and 92% after 10 days. Other findings revealed that 60 minutes after a 10-minute exposure to the EO/LP solution, 100% of the body lice were moribund or dead; all the body lice immersed in water were alive. The authors conclude that compared with the water treatment, the EO/LP solution was 100% effective in killing lice (P<0.0001).

The authors attribute the treatment failures seen in 7 of the 40 subjects in the EO/LP group in trial 1 to the fact that some lice or some eggs survived any 1 of the 3 treatments or that re-infestation occurred. After observing the results of the in vitro studies revealing “that the EO/LP solution is 100% ovicidal after only a 10-s immersion, it is more likely that the treatment failures are due to re-infestation,” they write.

The authors conclude that “the EO/LP solution contains a proprietary combination of essential oils that has been shown to be safe and effective in eliminating head lice in Australia,” and because the solution is both volatile and quickly effective, “it is unlikely to cause the development of head lice resistance in the community.”

Resource:

Greive KA, Barnes TM. The efficacy of Australian essential oils for the treatment of head lice infestation in children: a randomized controlled trial. Australas J Dermatol. March 7, 2017; [epub ahead of print]. doi: 10.1111/ajd.12626.

 

Flow Injection Mass Spectrometry, Proton Nuclear Magnetic Resonance, and DNA Sequencing Can All Distinguish Black Cohosh from Likely Adulterants

Harnly J, Chen P, Sun J, et al. Comparison of flow injection MS, NMR, and DNA sequencing: methods for identification and authentication of black cohosh (Actaea racemosa). Planta Med. February 2016;82(3):250-262. doi: 10.1055/s-0035-1558113.

Authentication and correct identification of botanicals in dietary supplements are critical for a number of reasons, not the least of which is potential harm from the inclusion of undesirable species. The process of identification may be complicated by material processing, variable preparation methods, and the existence of very similar related species. Current methods for identification of botanicals include morphological identification, DNA sequencing, and phytochemical and metabolic fingerprinting. As black cohosh (Actaea racemosa syn. Cimicifuga racemosa, Ranunculaceae) is a popular medicinal plant, adulteration is increasingly common. This basic research study coupled two methods of phytochemical fingerprinting, flow injection mass spectrometry (FIMS) and proton nuclear magnetic resonance (1H NMR), with DNA sequencing to determine how well they could identify different species of Actaea before and after processing.

Root samples from various species of Actaea were procured from American Herbal Pharmacopoeia (AHP), Scotts Valley, California; Strategic Sourcing, Inc., Banner Elk, North Carolina; The North Carolina Arboretum Germplasm Repository (TNCAGR), Asheville, North Carolina; National Institutes of Standards and Technology, Gaithersburg, Maryland; and from Chinese commercial sources. Liquids, tablets, and capsules were bought from local stores in Maryland, and additional samples were obtained from the United States Department of Agriculture, Washington D.C. The roots and commercial samples were authenticated using DNA sequencing at AuthenTechnologies LLC; Richmond, California. DNA sequences from the nuclear ribosomal internal transcribed spacer (ITS) region and the chloroplast psbA-trnH intergenic spacer, obtained by polymerase chain reaction (PCR) and Sanger capillary sequencing, were used for authentication by comparing them to the reference sequences. To prepare samples for FIMS, root material, tablets, and contents of capsules were powdered and extracted in 70:30 methanol:water, sonicated, centrifuged, diluted 1:10 with methanol, and filtered. Liquid extracts were combined with 70:30 methanol:water and treated as described above. To prepare for NMR, samples were dissolved in dimethyl sulfoxide-d6 containing 0.47 mM 4,4-dimethyl-4-silapentane-1-sulfonic acid, vortexed, sonicated, and centrifuged.

Each sample was run on FIMS five times, with random sample order each time; most samples were run once for NMR. Raw data were exported into various computer programs for analysis. Data were normalized to unit vector length (this metric incorporates the sum of squares) and analyzed using principal component analysis (PCA, an analysis that displays data based on greatest variation) and four multivariate analysis methods, especially soft independent modeling of class analogy (SIMCA, an analysis based on modeling that fits a model to a single class, which is explained to be useful for authentication). Both methods of analysis were used to assess whether FIMS or NMR could distinguish various Actaea species. Because of the complexity of PCA plots in including all samples, the authors chose to analyze the data from only the following five American species: black cohosh, bugbane (A. cimicifuga), baneberry (A. pachypoda), American bugbane (A. podocarpa), and red baneberry (A. rubra).

In analyses of both FIMS and NMR data, samples of black cohosh generally clustered separately from other species; some analyses portray it as most similar to baneberry, suggesting a close relation, and more distant from other species. One sample of black cohosh was found to occur outside the black cohosh cluster, and one sample of baneberry clustered with black cohosh; repeated analyses starting from new raw material had the same result. Significant phytochemical variation was observed within species; in the FIMS analysis, samples from multiple sites supplied by TNCAGR clustered according to the site of origin. The authors noted that the potential causes of geographically correlated variation include not only genetic differences and environmental influences on the plants but variation in the presence of endophytic fungi, which are suspected of producing some of the secondary compounds in black cohosh. The models for FIMS and NMR were validated using bootstrap analysis, despite the authors’ concern about limited sample size. It was found that FIMS had a sensitivity of 91.4% and NMR had a sensitivity of 91.7%, with specificities of 100% for both. Overall, it was concluded that both FIMS and NMR are appropriate techniques for distinguishing the five species of Actaea, with sensitivity to the phytochemical composition.

For North American samples of multiple species, putative identities according to DNA sequencing were generally consistent with the AHP identification, although sequencing quality problems sometimes precluded identification. The two samples that seemed to be outliers (black cohosh and baneberry) in the FIMS and NMR analyses had DNA sequences consistent with the stated identity. This suggests that the species are biologically complex species with morphological or chemical variations greater than the genetic variations. Very few of the geographically diverse black cohosh samples from TNCAGR, which were subjected to chemical analysis, were included in DNA analyses.

Root samples procured from China were stated to belong to four different species;

nuclear ribosomal DNA (nrDNA) and chloroplast DNA (cpDNA) sequences indicated that the majority of samples, including one purported sample of A. racemosa, were Chinese cimicifuga (A. dahurica) and one was A. brachycarpa, while two contained non-Actaea spp. plant material and another had only fungal DNA amplified. All of these, as well as some North American Actaea spp. samples were said to be “mixtures” according to ITS data, and to some extent according to psbA-trnH data; it appears that this simply means that more than one ITS sequence variant was present in some samples, while other samples may contain hybrid plant material. DNA analysis confirmed that four of the seven capsule supplements purchased locally contained black cohosh, while one contained A. brachycarpa; the other two had no detectable Actaea spp. DNA (one had no DNA and the other had rice [Oryza sativa, Poaceae] DNA or excipient DNA only). Liquid extract supplements were not analyzed with DNA sequencing since they were not expected to contain retrievable DNA. In summary, the FIMS and NMR analyses showed diverse chemical profiles that were different from any of the raw materials tested, which is presumably due to differences in processing and extraction methods or systematic geographical variations. Moreover, the DNA sequencing of roots could be used for identification of Actaea species and also for validating the discrepancies that might arise in the chemical fingerprinting methods.

In conclusion, the three methods outlined here may be useful to aid in authentication of black cohosh in commerce and identify possible adulterants. However, more experimentation and adjustment of methods would be necessary to analyze finished botanical supplements.

Bulletin on Adulteration of Scutellaria lateriflora

Goal:

The goal of this bulletin is to provide timely information and/or updates on issues of adulteration of Scutellaria lateriflora to the international herbal products industry and extended natural products community in general.

1 General Information

1.1 Common name: Skullcap3

1.2 Other common names:

English: Blue skullcap, helmet flower, hoodwort, European or greater skullcap, Quaker bonnet, mad-dog skullcap, mad weed, scullcap, Virginia skullcap4

French: Scutellaire, scutellaire latériflore, scutellaire de Virginie, toque, toque casquée5

German: Helmkraut, seitenblütiges Helmkraut5

Italian: Scutellaria

Spanish: Escutelaria, escutelaria de Virginia

1.3 Accepted Latin binomial: Scutellaria lateriflora L.6,7

1.4 Synonyms: Cassida lateriflora (L.) Moench; Scutellaria polybotrya Bernh.6,7

1.5 Botanical family: Lamiaceae (formerly Labiatae)

1.6 Plant part and form: The flowering aerial parts of S. lateriflora are used fresh, or dried as an infusion, as a tincture, or in the form of a fluid extract.1 Suggested daily dosages vary depending on the author and correspond to 0.25-12 g of dried aboveground flowering parts.1,8,9

1.7 General use(s): Traditionally, skullcap is used to help relieve nervousness and anxiety, as a sleep aid (mainly for stress-related cases of insomnia), or as an antispasmodic.1,7,8

2 Market

2.1 Importance in the trade: Skullcap is not a widely traded botanical commodity. In 2001, approximately 16 tons (35,000 pounds) of material were reportedly harvested and sold worldwide.10 No statistics on more recent volumes of harvested skullcap material could be identified in the published literature. The limited popularity of the herb is also shown by recent sales data from the United States (Table1), where it ranked between #99 and #107 of all single herbal dietary supplements in the Natural retail channel, and between #149 and #157 in the Mainstream Multi-Outlet retail channel. (T. Smith e-mail to S. Gafner, September 2, 2015 and September 3, 2015)

Table 1: Sales data for skullcap dietary supplements from 2012-2014.

Channel 2012 2013 2014
Rank Sales [US$] Rank Sales [US$] Rank Sales [US$]
Naturala 107 556,856 106 577,065 99 625,734
Mainstream Multi-Outletb n/a 19,355 157 22,735 149 27,997

aAccording to SPINS (SPINS does not track Whole Foods Market sales, which is a major natural products retailer in the US)

bAccording to SPINS/IRI (the Mainstream Multi-Outlet channel was formerly known as food, drug and mass market channel [FDM], exclusive of possible sales at Walmart)
n/a: not available
Source: T. Smith (American Botanical Council) e-mail September 2, 2015 and September 3, 2015

2.2 Supply sources: Most supplies on the North American market appear to be obtained from cultivated sources both in the United States (e.g., Minnesota, Missouri, North Carolina, Oregon, and Washington) and internationally (e.g., Chile, Costa Rica, and Mexico).11 According to a report for the Australian government, Australian growers formerly supplied skullcap, but production halted after 2003 when global prices dropped and local growers were not able to compete with the prices from abroad.12 The majority of the skullcap used in products sold in Australia is now imported (Hans Wohlmuth e-mail to S. Gafner, January 19, 2015). There is some commercial material available that is harvested in the wild in North America, but the majority (85% according to a report from 2001) is obtained from cultivation.10

2.3 Raw material forms: In the United States, many companies that manufacture products containing properly authenticated skullcap grow it themselves.11 Bulk skullcap raw material is mainly sold as cut and sifted, in form of a teabag cut, or as powdered aboveground parts, which may be more susceptible to adulteration, since the distinct features for macroscopic identification are no longer recognizable.

2.4 Market dynamics: In 2001, an estimated 16 tons of skullcap were harvested and sold on world markets at a price of US $9-13/kg.10 Since the cessation of production in Australia, prices for imported skullcap from North America have been gradually increasing and reached Australian (AUD) $42/kg (US $31/kg based on the exchange rate from June 1, 2006) for organic crops and AUD 25-30/kg (US $19-22/kg) for conventional crops in 2006.12 Based on a 2008 newsletter of the Australian raw material supplier Network Nutrition, growers in the United States have experienced issues with cultivation due to difficulties with seed germination, crop failure, and various other issues. This has led to a shortage in raw material and the appearance of material where skullcap was substituted with other species of Scutellaria.13 In recent years, the demand for skullcap has been has been subject to fluctuations but overall trended flat or was slightly increasing. Currently, growers under contract can obtain between US $18-19/kg for conventional and US $24-29/kg for certified organic skullcap (E. Fletcher e-mail to S. Gafner, January 20, 2015; L. Ballard oral communication to S. Gafner, January 28, 2015). Pricing for the consumer is in the range of US $43-47/kg for conventionally-grown herb and US $70-110/kg for organically grown skullcap, according to an informal survey, by co-author of this Bulletin (SG), of smaller companies that had listed pricing on the Internet.

  1. Adulteration

3.1 Known adulterants: Canada germander (Teucrium canadense, Lamiaceae); germander (T. chamaedrys); Scutellaria spp., e.g., Alpine skullcap (S. alpina), Chinese skullcap (S. baicalensis), hoary skullcap (S. incana), heartleaf skullcap (S. ovata), and marsh skullcap (S. galericulata).1,8

3.2 Sources of information confirming adulteration: The most comprehensive review on adulteration of skullcap has been published by Foster in HerbalGram for the ABC-AHP-NCNPR Botanical Adulterants Program.2 Other sources for information on skullcap adulteration include the American Herbal Pharmacopoeia monograph on Scutellaria lateriflora by Upton et al.,1 and the PhD thesis by Brock.8 Some of the adulteration seems to be due to the sale of mislabeled seed material, e.g., the inadvertent cultivation of S. incana in North America, or of S. ovata in the United Kingdom. 1,8 Leroy Ballard, president at Nature’s Cathedral, Inc., an American grower and supplier of native American medicinal plants, commented that there are still between 1350 and 1800 kg (3000 and 4000 lbs) of S. incana sold as “Scutellaria spp.” in the United States, but most of this material is exported overseas. (L. Ballard oral communication to S. Gafner, January 28, 2015). According to Brock, it is not clear how much of the skullcap material used by herbalists in the UK is actually S. ovata.8 Further evidence of ongoing adulteration of skullcap products available in the US market is demonstrated by the results from a study in 2011 by researchers at the United States Department of Agriculture, where 5 out of 13 commercial dietary supplements from US manufacturers purchased on the Internet were adulterated, reportedly with Canada germander and Chinese skullcap.14 [Note: The original publication does not state the source of the purchased products, but one of the authors has confirmed that they were from American (US) manufacturers. (P. Chen e-mail to S. Gafner, September 4, 2015)] Adulteration of commercially sold skullcap raw material with germander (species not identified) was also reported in 2012 by Walker and Applequist.15 Germander was formerly sold routinely as a bulk botanical in the United States but it is no longer offered by most herbal suppliers in the North American market (L. Ballard oral communication to S. Gafner, January 28, 2015).

3.3 Accidental or intentional adulteration: As indicated above, some of the adulterated material on the market may be due to rare accidental misidentification when material is harvested in the wild, or the cultivation of crops where the seeds have been mislabeled, which is likely the case for some of the adulteration with other species from the genus Scutellaria (except adulteration with Chinese skullcap, S. baicalensis, which does not grow in the same geographical area as S. lateriflora). The reasons behind the adulteration of skullcap with germander species is a matter of debate. Some experts suggest that it is accidental, but it is now believed that at least part of the adulteration is deliberate since the Teucriumspecies have a heavier dry weight than skullcap and therefore, a much higher yield is obtained when harvesting germander (E. Fletcher e-mail to S. Gafner , January 20, 2015; A. Chandra, e-mail to S. Gafner, January 23, 2015).12,16 Nomenclatural confusion may also play a roles, as pink skullcap is a common name applied to Canada germander.2

3.4 Frequency of occurrence: There is no comprehensive published study on the frequency of skullcap adulteration. The only study looking at the adulteration of skullcap dietary supplements included a limited amount of samples (n = 13) from manufacturers in the United States purchased over the Internet.14 In this study, 38% of the samples were found to be adulterated. On the other hand, a study looking at whole or minimally processed skullcap raw materials (n = 10) purchased from vendors within the United States, did not find any adulterated material, although the authors of the study specify that they “have seen a recent sample of commercial skullcap, not included within this study, that was over 50% Teucrium”.15 Similarly, a study investigating the authenticity of 11 commercial dietary supplements (10 extracts and one product made with crude powdered material) sold in the United States, using species-specific DNA primers, concluded that all nine samples from which DNA was obtained contained S. lateriflora. Two samples, including the product made with powdered raw herb, did not contain DNA of sufficient quality to determine the identity of the material (D. Harbaugh Reynaud e-mail to S. Gafner, January 14, 2016). No chemical assays were performed on these samples to confirm the results.

3.5 Possible safety/therapeutic issues: Substitution of S. lateriflora was a prominent issue in 2002 due to an Australian herbal product’s being implicated in the death of a patient due to liver failure.17According to the label, the herbal product contained kava (Piper methysticum, Piperaceae), passionflower (Passiflora incarnata, Passifloraceae) and skullcap. The authors of the case report suggested that the liver failure was possibly due to the ingestion of kava, a botanical that has been linked to rare occurrences of liver toxicity.18 However, the causative agent for the death of the Australian patient was never confirmed. The Australian Therapeutics Goods Administration (TGA) analyzed the product and determined that it did not contain skullcap. Some of the known skullcap adulterants, Teucrium species are known to cause liver injury in humans.19 The hepatotoxicity in Teucrium has been ascribed to the diterpenoid fraction.20 The liver toxicity of germander is influenced by a number of factors, including the diet, the type of germander preparation, and possibly genetic factors.21,22 In contrast to many of the germander neo-clerodane diterpenes, those with a tetrahydrofuran moiety did not show hepatotoxic effects. The neo-clerodane diterpenes isolated from skullcap by Bruno et al.23 are different since they are substituted with either a dihydrofuran-fused tetrahydrofuran moiety or a fused tetrahydrofuran-γ-lactone ring. The detection of these specific diterpenes may offer a way to uncover adulteration, although subsequent studies failed to detect diterpenes in skullcap.24,25

The root of Chinese skullcap (S. baicalensis) is widely used in Traditional Chinese Medicine. There are some reports of allergic reactions, diarrhea, and stomach discomfort after ingestion or injection of Chinese skullcap.26 There are also a small number of case reports that have linked Chinese skullcap to liver injury,27,28 but this implication is based on previous reports where causality between Chinese skullcap ingestion and liver injury reportedly has not been established,29 or on case reports implicating a proprietary mixture of flavonoids from Chinese skullcap, catechins from betelnut palm (Areca catechu, Arecaceae), and zinc bisglycinate sold as a medical food under the brand name Limbrel® (Primus Pharmaceuticals, Phoenix, AZ).28 Aboveground parts of barbed skullcap (S. barbata), a skullcap species native to China, are similarly used and theoretically could be substituted for S. lateriflora, though this has not been formally reported. Since S. lateriflora does not grow naturally in China, and based on current knowledge, is not generally cultivated there, there is a greater likelihood that attempts by companies to procure S. lateriflora from Chinese suppliers could result in use of Chinese species.

The substitution of skullcap with material from other species of Scutellaria does not pose an apparent safety risk, although the data on use in humans with the adulterating species is more limited. Scutellaria galericulata, which is also used in herbal medicine, is believed to have similar actions and indications as S. lateriflora.16 The ethnobotanical use of S. galericulata and S. incana in North America is described by Moerman.30 Scutellaria galericulata herb has been used by the Delaware tribe of Native Americans as a gastrointestinal aid and a laxative. The Ojibwe tribe used the aboveground parts for heart trouble.Scutellaria incana decoctions were used by the Cherokee as abortifacient, to treat diarrhea, against breast pain and as a gynecological aid, but ethnobotanical research suggests that Native American tribes used the root of the plant rather than the aboveground parts.30 In addition, the chemical composition of these species, with the exception of the flavonoids, has not been established in detail.

3.6 Analytical methods to detect adulteration: Confirmation of species identity and purity may be achieved by organoleptic methods, if conducted by qualified personnel (e.g., a botanist) for plant material in its whole form. For establishing the identity of cut or powdered raw material, a combination of a physical assessment test (e.g., macroscopic or microscopic) with chemical identification methods or a suitable genetic approach is considered appropriate. Results from a paper using species-specific primers to authenticate commercial skullcap supplements had a success rate of finding skullcap DNA in nine out of 11 products (82%) with the remainder not containing any identifiable DNA. Chromatographic methods, such as high-performance thin-layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC), can be used for chemical characterization of raw material and extracts. A comprehensive evaluation of publicly available methods for the authentication of skullcap and detection of adulterants in skullcap, the Skullcap Laboratory Guidance Document, is available through the ABC-AHP-NCNPR Botanical Adulterations Program website.31

3.7 Perspectives: Industry expert Steven Foster, president of Steven Foster Group, Inc., believes that “there is no accidental misidentification of Teucrium canadense as Scutellaria lateriflora. That is a myth. One can easily harvest a pick-up truck load of T. canadense in a morning, whereas one would be hard-pressed to harvest a few pounds of any Scutellaria spp. from any wild habitat anywhere in the United States in a day. The adulteration of Scutellaria lateriflora with Teucrium canadense is pure and simple ‘under the radar’ economic adulteration.” (S. Foster, e-mail to S. Gafner, January 28, 2015)

4 Conclusions

Based on a survey in the United Kingdom,32 skullcap is a highly regarded medicinal herb with herbal medicine practitioners. It has remained relatively popular in the United States as a botanical to treat anxiety and stress-related conditions.1 The substitution of skullcap with germander species is particularly deplorable because of the known toxicity of species of plants in the genus Teucrium. Such adulteration is easily detected by a variety of analytical methods, a detailed report of which is available in the Skullcap Laboratory Guidance Document,31 and as such, the potentially dangerous presence of Teucrium material labelled as skullcap in botanical raw materials or finished products cannot be excused.

5 References

  1. Upton R, Graff A, Soria T, Swisher D. American Herbal Pharmacopoeia and Therapeutic Compendium: Skullcap Aerial Parts: Scutellaria lateriflora L.: Standards of Analysis, Quality Control and Therapeutics. Scotts Valley, CA: American Herbal Pharmacopoeia; 2009.
  2. Foster S. Adulteration of skullcap with American germander. HerbalGram. 2012:(93);34-41. Available at: http://cms.herbalgram.org/herbalgram/issue93/FEAT_skullgerm.html. Accessed April 21, 2016.
  3. McGuffin M, Kartesz JT, Leung AY, Tucker AO. American Herbal Products Association’s Herbs of Commerce. 2nd ed. Silver Spring, MD: American Herbal Products Association; 2000.
  4. Gruenwald J, Brendler T, Jaenicke C, et al. (eds). PDR for Herbal Medicines, 2nd ed. Montvale, NY: Medical Economics Co; 2000:678.
  5. The Plant List. Version 1.1 (September 2013). Available at: http://www.theplantlist.org. Accessed April 21, 2016.
  6. List PH, Hörhammer L. Scutellaria. In: Hager’s Handbuch der Pharmazeutischen Praxis, Volume 6. Berlin: Springer Verlag; 1979:339-341.
  7. Tropicos.org. Missouri Botanical Garden. Available at: http://www.tropicos.org. Accessed April 21, 2016.
  8. Brock CA. American skullcap (Scutellaria lateriflora L.): a study on its effects on mood in healthy volunteers. PhD thesis. London: University of Westminster; 2012. Available at: http://westminsterresearch.wmin.ac.uk/12194/1/Christine_BROCK.pdf. Accessed April 21, 2016.
  9. Health Canada: Natural Health Products Ingredients Database. Skullcap. Available at: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/monoReq.do?id=159. Accessed April 21, 2016.
  10. Greenfield J, Davis JM. Medicinal Herb Production Guide: Skullcap (Scutellaria lateriflora L.). Chapel Hill, NC: North Carolina Consortium on Natural Medicines; 2004.
  11. Upton R. Skullcap Scutellaria lateriflora L.: An American nervine. J Herb Med. 2012;2(3):76-96.
  12. Yap G. Prospects for medicinal herbs: Assessment of market potential for selected medicinal herb products (Valerian, Arnica, Skullcap, Echinacea, Goldenseal). Barton, Australia: RIRDC. 2006.
  13. Gorman R. Buyer Beware: Scutellaria lateriflora. In: Nutralink. Network Nutrition Pty Ltd, Australia. 2008. Available at: http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCAQFjAA&url=http%3A%2F%2Fnetworknutrition.com.au%2Fcontent.cfm%3FLive%3D0%26ContentType%3DContent%26ContentID%3D84%26TEI%3D150%26TLI%3D0&ei=SEvJVMOXLu3GsQS0p4G4CQ&usg=AFQjCNFc5twJHGECqPA0znGIXbB62biP3Q&sig2=d4U1iWtoAjBOTAZvJU3MxA. Accessed April 21, 2016.
  14. Sun J, Chen P. A flow-injection mass spectrometry fingerprinting method for authentication and quality assessment of Scutellaria lateriflora-based dietary supplements. Anal Bioanal Chem.2011;401(5):1577-1584.
  15. Walker KM, Applequist WL. Adulteration of selected unprocessed botanicals in the U.S. retail herbal trade. Econ Bot. 2012;66(4):321-327.
  16. Wills RBH, Stuart DL. Generation of high quality Australian skullcap products. Barton, Australia: RIRDC. 2004. Available from: http://www.rirdc.gov.au/reports/EOI/04-020.pdf. Accessed April 21, 2016.
  17. Gow PJ, Connelly NJ, Hill RL, Crowley P, Angus PW. Fatal fulminant hepatic failure induced by a natural therapy containing kava. Med J Aust. 2003;178(9):442-443.
  18. Teschke R, Sarris J, Schweitzer I. Kava hepatotoxicity in traditional and modern use: the presumed Pacific kava paradox hypothesis revisited. Brit J Clin Pharmacol. 2012;73(2):170-174.
  19. Laliberte L, Villeneuve JP, 1996. Hepatitis after the use of germander, a herbal remedy. Can Med Assoc J. 1996;154(11):1689-1692.Opinion of the Scientific Committee on Food on teucrin A, major component of hydroalcoholic extracts of Teucrium chamaedrys (wild germander).
  20. European Commission, Health & Consumer Protection Directorate General. Opinion of the Scientific Committee on Food on teucrin A, major component of hydroalcoholic extracts of Teucrium chamaedrys (wild germander). Brussels, Belgium. 2003. Available at: http://ec.europa.eu/food/fs/sc/scf/out173_en.pdf. Accessed April 21, 2016.
  21. Nencini C, Galluzzi P, Pippi F, Menchiari A, Micheli L. Hepatotoxicity of Teucrium chamaedrys L. decoction: Role of difference in the harvesting area and preparation method. Ind J Pharmacol. 2014;46(2):181-184.
  22. Zhou S, Koh HL, Gao Y, Gong ZY, Lee EJ. Herbal bioactivation: The good, the bad and the ugly. Life Sci. 2004;74(8):935-968.
  23. Bruno M, Cruciata M, Bondi ML, et al. Neo-clerodane diterpenoids from Scutellaria lateriflora.Phytochemistry. 1998;48(4):687-691.
  24. Lin LZ, Harnly JM, Upton R. Comparison of the phenolic component profiles of skullcap (Scutellaria lateriflora) and germander (Teucrium canadense and T. chamaedrys), a potentially hepatotoxic adulterant. Phytochem Anal. 2009;20(4):298-306.
  25. Li J, Wang YH, Smillie TJ, Khan IA. Identification of phenolic compounds from Scutellaria laterifloraby liquid chromatography with ultraviolet photodiode array and electrospray ionization tandem mass spectrometry. J Pharm Biomed Anal. 2012;63:120-127.
  26. Gardner Z, McGuffin M (eds). American Herbal Products Association’s Botanical Safety Handbook. 2nded. Boca Raton, FL: CRC Press; 2013.
  27. Teschke R, Wolff A, Frenzel C, Schulze J. Herbal hepatotoxicity–an update on traditional Chinese medicine preparations. Aliment Pharmacol Ther. 2014;40:32-50.
  28. Chalasani N, Vuppalanchi R, Navarro VJ, et al. Acute liver injury due to Flavocoxid (limbrel), a medical food for osteoarthritis. A case series. Ann Intern Med. 2013;156: 857-860.
  29. Dhanasekaran R, Owens V, Sanchez W. Chinese skullcap in move free arthritis supplement causes drug induced liver injury and pulmonary infiltrates. Case Reports Hepatol. 2013;2013:965092.
  30. Moerman DE. Native American Ethnobotany. Portland, OR: Timber Press; 1988.
  31. Gafner S. Skullcap Adulteration Laboratory Guidance Document. Austin, TX: ABC-AHP-NCNPR Botanical Adulterants Program. 2015. Available at: http://cms.herbalgram.org/BAP/LGD/SkullcapLabGuidanceDocument.html. Accessed January 15, 2016.
  32. Brock C, Whitehouse J, Tewfik I, Towell T. The use of Scutellaria lateriflora: A pilot survey amongst herbal medicine practitioners. J Herb Med. 2012;2(2):34-41.

Bulletin on Adulteration of Hydrastis canadensis root and rhizome

Goal:

The goal of this bulletin is to provide information and/or updates on issues regarding adulteration of goldenseal (Hydrastis Canadensis) root to the international herbal industry and extended natural products community in general. It is intended to present the available data on the occurrence of adulteration, the market situation, and consequences for the consumer and the industry.

1 General Information

1.1 Common name: Goldenseal1,2

1.2 Other common names:

English: Yellow root, yellow puccoon, ground raspberry, wild curcuma*, Indian dye, eye root, eye balm, Indian paint, jaundice root, Warnera3,4

French: Hydraste du Canada, hydraste, fard inolien, framboise de terre, sceau d’or5

German: Goldsiegelwurzel, Kanadische Gelbwurz, Kanadische Orangenwurzel5

Italian: Idraste, radice gialla6

Spanish: Hidrastis, hidrastis de Canadá, raíz de oro, scello de oro5

1.3 Accepted Latin binomial: Hydrastis canadensis7,8

1.4 Botanical family: Ranunculaceae

1.5 Plant part and form: Whole fresh or dry roots and rhizomes, powdered dry roots and rhizomes, hydroalcoholic and glycerin-water extracts and powdered dry extracts.9,10 Dried whole or powdered roots and rhizomes complying with the United States Pharmacopeia (USP) are required to contain not less than 2.0% of hydrastine and not less than 2.5% berberine.10

1.6 General use(s): Native American tribes used goldenseal root and rhizome preparations as eye washes, treatments for skin disorders, bitter tonics, and for respiratory ailments and the infectious diseases brought by European settlers.11 The plant was included in The American Eclectic Materia Medica and Therapeutics12 and King’s American Dispensatory,13 which increased its use substantially among Eclectic physicians for infections, mouth ulcers, and thrush, inflamed mucous membranes, chronic gonorrhea, jaundice, gastrointestinal complaints, as a bitter tonic and as a uterine tonic. Goldenseal preparations are now used as antimicrobial agents to treat infections of the mucosal membrane, including mouth, upper respiratory tract, gastrointestinal tract, eyes, vagina, as well as for wounds.9

 

2 Market

2.1 Importance of the trade: Echinacea-goldenseal combination dietary supplements were ranked #15 in sales in the natural food channel in the United States in 2013 and in 2014 (Table 1), with estimated sales exceeding $5 million in 2014. Sales in the Mainstream Multi-Outlet retail channel (excluding sales data from Walmart and Club stores in 2013 and 2014, which were not available) were lower, with echinacea-goldenseal products ranking between #41 and #53. (T. Smith [American Botanical Council] e-mail to S. Gafner, September 2, 2015, and September 3, 2015)14,15

Goldenseal root/rhizome-only supplements did not rank in the top 50 best-selling herbal supplements in the natural food channel or the Mainstream Multi-Outlet retail channel from 2012-2014 (Table 2).

Table 1: Sales data for echinacea-goldenseal dietary supplements from 2012-2014. 

Channel 2012 2013 2014
Rank Sales [US$] Rank Sales [US$] Rank Sales [US$]
Naturala 18 4,400,290 15 4,824,801 15 5,116,708
Mainstream Multi-Outletb 41 2,665,724 53 1,697,591 53 1,566,916

Table 2: Sales data for goldenseal-only dietary supplements from 2012-2014.

Channel 2012 2013 2014
Rank Sales [US$] Rank Sales [US$] Rank Sales [US$]
Naturala 68 1,046,775 70 1,111,038 69 1,110,546
Mainstream Multi-Outletb 60 1,287, 453 106 217,617 102 207,312

aAccording to SPINS (SPINS does not track Whole Foods Market sales, which is a major natural products retailer in the US)
bAccording to SPINS/IRI (the Mainstream Multi-Outlet channel was formerly known as food, drug and mass market channel [FDM]; possible sales at Walmart and Club stores are excluded in 2013 and 2014)
n/a: not available
Source: T. Smith (American Botanical Council) e-mail September 2, 2015, and September 3, 2015

2.2 Supply sources: Historically, the majority of the goldenseal root and rhizome on the market has come from the wild-harvested material, with Kentucky and Tennessee as the major producers. Other states along the Appalachian Mountains and in the northeastern United States provide additional supplies.9 There is no credible evidence that H. Canadensis is cultivated commercially outside of the United States and Canada.

2.3 Conservation status: In 1997 goldenseal was listed on Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora,17 which also controls global trade and markets for H. Canadensis.18 Several states consider H. Canadensis in need of conservation: Pennsylvania lists the plant as vulnerable, at high risk of endangerment in the wild; Maryland, Michigan and New York list the plant as threatened, at risk of extinction in the wild sometime in the near future; Connecticut, Georgia, Massachusetts, Minnesota, New Jersey and Vermont list the plant as endangered, at high risk of extinction in the wild; North Carolina and Tennessee list the plant as endangered with special concern, at critically high risk of extinction in the wild.19

2.4 Raw material forms: Bulk goldenseal root and rhizome raw material is sold as whole roots and rhizomes (fresh or dry), cut and sifted, or as a powder.

2.5 Market dynamics: Despite a general trend of price increases since 1986, the costs vary considerably from year to year. Prices per kg paid to collectors of dried wild goldenseal root and rhizome ranged from the US $44–$77 between 1996 and 2005, and $77 wild to $110 for organic woods-cultivated material for the same time frame.20 The price per kg of dried wild root and rhizome peaked at $77 in 2001, dropping to $44 per kg in 2005, and fluctuating between $44–55 per kg through 2010.21 In its tonnage report, the American Herbal Products Association (AHPA) reported an average yearly harvest of 10 metric tons (MT) of cultivated compared to 30 MT of wild-harvested dry goldenseal root and rhizome between 2004 and 2010. The amounts of fresh goldenseal root and rhizome have remained below one MT in the same timeframe. Generally, the quantities of goldenseal root and rhizome harvested between 2004 and 2010 have been relatively steady.22

3 Adulteration

3.1 Historical adulterants: At the height of the Eclectic medical movement in the United States during the early 1900s, the price of goldenseal had risen to the point that several plant species were being used as economic adulterants on a regular basis; these included goldthread or coptis (Coptis spp., Ranunculaceae), yellow root (Xanthorrhiza simplicissima, Ranunculaceae), European peony (Paeonia Officinalis, Paeoniaceae),and twin leaf (Jeffersonia diphylla, Berberidaceae).23,24 The adulteration of goldenseal with Virginia snakeroot (Aristolochia serpentaria, Aristolochiaceae), which is of concern due to its content of nephrotoxic and carcinogenic aristolochic acids, was initially documented in 1892 and described again in 1900.25 However, there are no reported cases of adulteration with Virginia snakeroot in recent times. Additional historical adulterants and contaminants of goldenseal that have been documented include Athyrium filix-femina (Athyriaceae), Stylophorum diphyllum (Papaveraceae), Cypripedium calceolus(Orchidaceae), Collinsonia canadensis (Lamiaceae), Trillium spp. (Melanthiaceae), Caulophyllum thalictroides (Berberidaceae), and Polygala senega (Polygalaceae) as admixtures or contaminants.26 It is unlikely that adulteration is occurring with these species in commerce today.

3.2 Recent adulterants: Over the past 20–30 years, economic adulterants have reappeared in goldenseal products,27-29 based in part on the erroneous use of goldenseal to negate illicit drug testing in the 1980s.30 The adulterating species include Japanese goldthread (Coptis japonica), yellow root (Xanthorrhizasimplicissima), Oregon grape (Mahonia aquifolium, Berberidaceae), celandine (Chelidonium majus, Papaveraceae), barberry (Berberis spp., Berberidaceae), and yellow dock (Rumex spp., Polygonaceae) root.2,9,27 There is a single case of the sale of other root materials labeled as goldenseal, e.g., plantain (Plantago spp., Plantaginaceae) root, nettle (Urtica dioica, Urticaceae) root, or passionflower (Passiflora incarnata, Passifloraceae) root colored with a yellow dye, as reported on the website of an analytical laboratory.31

Historically, market pricing for H. Canadensis has displayed instability.20 As noted above, over the more recent 15 years the price has ranged between $44-110/kg for dry root and rhizome material. Assuming that the relatively higher goldenseal price level drives intentional economic adulteration, the addition and/or substitution with several of the adulterating plant species would represent substantial cost savings to an unscrupulous supplier. Over the past 20 years, dried roots of the species Mahonia have sold at $6.1-$8.8 per kg and Berberis at $7.3-14.30 per kg. Over the past 10 years, the price/kg of adulterating species ranged as follows: celandine $3.7-6.9, barberry $5.6-19.3, yellow dock imported $9.5-10.1 and domestically grown $12.9-14.8. (S. Yeager [Mountain Rose Herbs] e-mail, August 25, 2015) The price/kg for Coptis spp. was approximate $14.1 per kg in 2011 and $11.0/kg in 2015.32

3.3 Sources of information supporting confirmation of adulteration: Goldenseal adulteration can be detected through the presence or absence of several alkaloids, namely the presence of berberine, canadine, hydrastine, and hydrastinine, and the absence of palmatine.9 Although most species used as adulterants contain berberine, the alkaloids hydrastine and canadine are unique to goldenseal.9 The presence of palmatine is indicative of adulteration by Coptis spp., the most common adulterant of goldenseal.27 An analysis of several dietary supplement products marketed as goldenseal root extract using the AOAC official method 2008.04-2008, a high-performance liquid chromatography (HPLC) method for the analysis of goldenseal material, revealed that several products contained palmatine.33

A validated HPLC-mass spectrometry (MS) method was used to analyze H. Canadensis root from three suppliers along with the common adulterants – Coptis spp. root, M. aquifolium root, Berberis spp. bark, and C. majus herb.29 Of the three commercial lots that were purchased, all contained the expected goldenseal alkaloids: hydrastinine berberastine, tetrahydroberberastine, canadaline, berberine, hydrastine, and canadine. However, one product contained additional alkaloids not associated with goldenseal – palmatine, coptisine, and jatrorrhizine – thus suggesting admixture of an adulterating species. Avula et al. used an ultra-high-performance liquid chromatography (UHPLC) method to detect the non-goldenseal constituents palmatine, coptisine, and jatrorrhizine in a commercial goldenseal product.34 An emerging adulterant problem stems from the use of goldenseal leaf material, which contains both berberine and hydrastine, but in a different ratio from goldenseal root.27

 

A recent report by a company specializing in DNA-based species identification analyzed several off-the-shelf goldenseal products, including those from a company described as “a major manufacturer.” The company used their proprietary ConfirmIDNATM method, a DNA barcoding method using universal primers, to identify plantain root, nettle root, or passionflower root rather than goldenseal. In addition, the product was colored with a yellow dye.31 No additional tests were carried out to confirm these findings.

Although this publication is focused on H. Canadensis root, commercial trade in H. Canadensis leaf does occur. Dried leaf harvest for the years 2004-2010 was estimated to range from 3.5-8.5 MT.22 During that time the price was approximate $2.2-11.0/kg (E. Burkhart [Pennsylvania State University] e-mail, September 21, 2012). Goldenseal leaf is an article of commerce, and there are allegations of its use as a low-cost adulterant.27 Actual evidence of non-declared goldenseal leaf as an adulterant to goldenseal root/rhizome is rare. One analysis of hydrastine and berberine in goldenseal leaf found levels of these alkaloids ranging at 0.27-0.29% and 0.36-0.39%, respectively, while levels in the root were 2.25-3.32% and 2.61-3.75%, respectively. As part of this 2002 study, three commercial echinacea/goldenseal products were tested with one containing only berberine in the expected range of goldenseal-derived isoquinoline alkaloids, which may indicate an adulterant species was used. Another contained very low alkaloid content suggesting possible leaf adulteration.29

 

3.4 Accidental or intentional adulteration: Historically as well as recently, the use of adulterating species appears to be motivated primarily by economic gain,24-29 particularly when bulk goldenseal root is selling for up to $110 per kg.

3.5 Frequency of occurrence: There is no comprehensive study on the frequency of goldenseal adulteration. One analysis in 2003 of three lots of purchased commercial goldenseal root powder found goldenseal alkaloids hydrastinine, berberastine, tetrahydroberberastine, canadaline, berberine, hydrastine, and canadine in all samples, while only one sample from a single supplier also contained palmatine, coptisine, and jatrorrhizine, presumably indicating that adulteration with coptis occurred in that one sample.29

3.6 Possible therapeutic/safety issues: Although no systematic investigation into human toxic effects associated with the use of Berberis spp., Coptis spp., or M. aquifolium could be found, no other spontaneous or anecdotal reports of adverse effects could be found. The second edition of the American Herbal Products Association’s Botanical Safety Handbook (BSH2) lists B. Vulgaris and C. Chinensis as class 2b safety ingredients, meaning that these botanicals should not be used during pregnancy. The safety concerns in the BSH2 are based on studies using pure berberine, and may not directly apply to extracts made from barberry or coptis. Mahonia aquifolium, which also contains berberine, is presented as a safety class 1 ingredient, which is a botanical that is considered to be safe when used appropriately. Nevertheless, use of Oregon grape during pregnancy is not recommended. In addition, all berberine-containing plants are not recommended for use during lactation.35

Case studies of Chelidonium majus herb in Germany have associated consumption of the herb with liver toxicity. Ad hoc causality assessments in 22 spontaneous cases employing a liver-specific, standardized, quantitative assessment method (Council for International Organizations of Medical Sciences) found causality to be highly probable (n = 2), probable (n = 6), possible (n = 10), unlikely (n = 1), and excluded (n = 3). The pattern of liver injury was observed predominantly among female consumers. The average treatment was 36.4 days, and the latency period until first symptoms and jaundice was 29.8 and 35.6 days, respectively. The study did not identify which of the constituents were responsible for the liver injury.36 No product analysis was conducted and manufacturer observance of cGMP (current Good Manufacturing Practices) was assumed. As such, it is unknown if adulterated products impacted the reported adverse effects.

3.7 Analytical methods to detect adulteration: Brown and Roman conducted a multi-laboratory collaborative study utilizing an HPLC-ultraviolet (UV) detection method, previously validated using AOAC International single-laboratory validation guidelines, to measure hydrastine and berberine in goldenseal root raw materials, extracts, and dietary supplements at concentrations of 0.4 to 6% (w/w). In addition to the quantification of berberine and hydrastine, the method also detected the presence of palmatine, an indicator of adulteration with Coptis spp.33 Based on the results of the study the method was subsequently adopted as AOAC official method 2008.04-2008.37 Weber et al., generated different alkaloid profiles for H. Canadensis root and two berberine-containing Coptis species using a validated HPLC-MS method.38 Kamath and colleagues investigated alkaloid compositions of H. Canadensis, American goldthread (C. trifolia) and coptis (C. Chinensis). They determined that the spectrum of alkaloids in C. Chinensis was different from those in H. Canadensis and C. trifolia, showing that the alkaloid fingerprint was suitable to distinguish the species.39 Another HPLC-MS method was shown to separate 10 analytes (berbamine, berberine, canadine, chelerythrine, coptisine, hydrastinine, hydrastine, jatrorrhizine, palmatine, and sanguinarine) from six different plant species (H. Canadensis, Coptis japonica, B. vulgaris, Chelidonium majus, M. aquifolium andS. Canadensis), allowing analysts to quantify the presence of adulterants at concentrations as low as 5%.40More recently, a UPLC method with UV detection was used to identify the non-goldenseal constituents palmatine, coptisine, and jatrorrhizine in a commercial goldenseal product.34

Govindan and Govindan developed a thin-layer chromatography (TLC) method to detect hydrastine, hydrastinine, and berberine of several goldenseal preparations.41 Their analysis identified three samples containing only berberine and one sample that contained none of the alkaloids, potentially indicating economic adulteration. The results of the TLC analysis were confirmed by subsequent HPLC tests.41 The American Herbal Pharmacopoeia adopted a validated high-performance TLC (HPTLC) method that simultaneously detects palmatine, which is found in adulterants, plus berberine, hydrastine, and hydrastinine. Upton noted the usefulness of hydrastinine as a reliable marker for old or poor quality H. Canadensis, since it is formed as a degradation product of hydrastine.42 Finally, a TLC/desorption electrospray ionization (DESI)-MS method was shown to detect non-goldenseal alkaloids from adulterants in goldenseal products.43

Several official compendial methods exist that may also be applied to adulterant detection, including theEuropean Pharmacopoeia44 and the United States Pharmacopeia–National Formulary.45 Criteria to perform identification using macroscopic and microscopic examinations of goldenseal rhizome and root are presented in several references.42,44,45 In addition to the macroscopic and microscopic characteristics of goldenseal, the AHP monograph also lists such characteristics for Oregon grape, Coptis spp., yellow dock, and yellow root.42

Other, unique analytical systems have been developed that detect both major and minor H. canadensis alkaloids. These methods, including capillary electrophoresis-mass spectrometry (CE-MS),46 pH-zone-refining counter-current chromatography (CCC),47 shift subtracted Raman spectroscopy (SSRS),48 and an enzyme-linked immunosorbent assay (ELISA) linked to an HPLC,49 may be adapted for the detection of adulterants.

4 Conclusions: Habitat destruction in some areas of the eastern United States, goldenseal’s native range, has decreased the availability of this important medicinal plant. Pricing pressure has historically increased the incentive for economically motivated adulteration of goldenseal root. Although the actual extent of adulteration of goldenseal root and rhizome in the current market is not clear, a number of authenticated methods exist to detect such adulteration, including some that have been validated.

*Although it has sometimes been called wild Curcuma, goldenseal should not be confused with turmeric root (Curcuma longa, Zingiberaceae).

5 References

  1. Barton BS. Collections for an Essay Towards a Materia Medica of the United States. Philadelphia, PA: Way & Groff. 1798 &1804 (Part Second). Reprint: Bulletin of the Lloyd Library No. 1 Reproduction Series No. 1;1900.
  2. McGuffin M, Kartesz JT, Leung AY, Tucker AO. Herbs of Commerce. 2nd ed. Silver Spring, MD: American Herbal Products Association; 2000.
  3. Grieve M. A Modern Herbal. Vol. 1. Mineola, NY: Dover Publications; 1971. Available at: http://www.botanical.com/botanical/mgmh/g/golsea27.html. Accessed July 16, 2015.
  4. Gruenwald J, Brendler T, Jaenicke C, et al., eds. PDR for Herbal Medicines. 2nd ed. Montvale, NJ: Medical Economics Company, Inc.; 2000.
  5. United States Department of Agriculture (USDA), Agricultural Research Service (ARS), National Genetic Resources Program. Germplasm Resources Information Network (GRIN) Online Database. Beltsville, MD: National Germplasm Resources Laboratory. Available at: http://www.ars-grin.gov/cgi-bin/npgs/html/taxon.pl?19478. Accessed July 20, 2015.
  6. Guareschi I, ed. Commentario della Farmacopea Italiana e dei Medicamenti in Generale. Vol. 2, part 1, commentario E-M. Torino, Italy: Unione Tipografico; 1897: 315-317.
  7. Linnaeus C. Systema Naturae. Vol. 2. 10th ed. Holmiae: Laurentii Salvii;1758.
  8. Hydrastis canadensis. The Plant List website. Available at: http://www.theplantlist.org/tpl1.1/record/tro-27100410. Accessed June 26, 2015.
  9. Upton R, Graff A, Swisher D. Goldenseal root, Hydrastis canadensis L.: Standards of Analysis, Quality Control, and Therapeutics. Santa Cruz, CA: American Herbal Pharmacopoeia; 2001.
  10. United States Pharmacopeial Convention. Powdered Goldenseal. In: USP 39-NF 34. Rockville, MD: United States Pharmacopeial Convention. 2016.
  11. Moerman DE. Medicinal Plants of Native America Vol. 1. Ann Arbor, MI: University of Michigan, Museum of Anthropology; 1988.
  12. Ellingwood F. American Materia Medica Therapeutics and Pharmacognosy.1919. Sandy, OR: Eclectic Medical Publications; 1983.
  13. Felter HW and Lloyd JU. King’s American Dispensatory. 1898. Sandy, OR: Eclectic Medical Publications; 1886.
  14. Lindstrom A, Ooyen C, Lynch ME, Blumenthal M, Kawa K. Sales of herbal dietary supplements increase by 7.9% in 2013, marking a decade of rising sales. HerbalGram. 2014;103:52-56. Available at: http://cms.herbalgram.org/herbalgram/issue103/HG103-mkrpt.html. Accessed May 19, 2016.
  15. Smith T, Lynch ME, Johnson J, Kawa K, Baumann H, Blumenthal M. Herbal dietary supplement sales in the US increase 6.8% in 2014. HerbalGram. 2015;107:52-59. Available at: http://cms.herbalgram.org/herbalgram/issue107/hg107-mktrpt-2014hmr.html. Accessed May 19, 2016.
  16. Oldfield S. IUCN/SSC Medicinal Plant Specialist Group PC 15 Inf. 3. Available at: http://www.cites.org/common/com/pc/15/X-PC15-03-Inf.pdf. Accessed July 26, 2015.
  17. CITES. Hydrastis Canadensis. Species database Available at http://www.cites.org/eng/app/appendices.php; 2012. Accessed July 17, 2015
  18. US Forest Service. Laws and regulations to protect endangered plants. The Convention on International Trade in Endangered Species of Wild Fauna and Flora. Available at: http://www.fs.fed.us/wildflowers/Rare_Plants/conservation/lawsandregulations.shtml. Accessed July 17, 2015.
  19. Plants Database [database online]. USDA Beltsville MD. Available at: http://www.embase.com.ezproxy.med.ucf.edu/home. Accessed July 16, 2015.
  20. Burkhart E. Goldenseal. Non-timber forest products (NTFPs) from Pennsylvania 2.  State College, PA: Information and Communication Technologies in the College of Agricultural Sciences, Penn State University.  Available at: http://extension.psu.edu/natural-resources/forests/botanicals/goldenseal/goldenseal; 2006. Accessed July 16, 2015.
  21. Pengelly A, Bennett K, Spelman K, Tims M. Appalachian plant monographs: Hydrastis Canadensis L., goldenseal. Appalachian Center for Ethnobotanical Studies; 2012. Available at http://www.frostburg.edu/fsu/assets/File/ACES/Hydrastis%20canadensis%20for%20ACES%20website.pdf. Accessed June 26, 2015.
  22. Dentali S, Zimmerman M. American Herbal Products Association Tonnage Surveys of Select North American Wild-Harvested Plants, 2006-2010. Silver Spring, MD: American Herbal Products Association; 2012.
  23. Lloyd JU, Lloyd CG. Drugs and Medicines of North America: Ranunculaceae. Cincinnati, OH: JU and CG Lloyd; 1884-85.
  24. Blaque G, Maheu J. Les falsifications actuelles de l’Hydrastis canadensis. Bull Sci Pharm. 1926;33,375-384.
  25. Collin ME. Note sur l’Hydrastis canadensis. J Pharm Chim. 1900;6(11):309-314.
  26. Blaschek W, Ebel S, Hackenthal E, et al., eds. Hydrastis rhizoma. In: HagerROM 2006: Hagers Handbuch der Drogen und Arzneistoffe. Version 5.0. Heidelberg, Germany: Springer Medizin Verlag. 2006.
  27. Betz JM, Musser SM, Larkin GM. Differentiation between goldenseal (Hydrastis Canadensis L.) and possible adulterants by LC/MS. Presented at: 39th Annual Meeting of the American Society of Pharmacognosy; July 1998; Orlando, FL.
  28. Wang MF, Zhu NQ, Jin Y, Belkowitz N, Ho CT. A Quantitative HPLC Method for the Quality Assurance of Goldenseal Products in the U.S. Market, in Quality Management of Nutraceuticals. In: Ho CT, Zheng Q, eds. ACS Symposium Series; 2002.
  29. Weber HA, Zart MK, Hodges AE, Molloy HM, O’Brien BM, Smith CS. Chemical comparison of goldenseal (Hydrastis Canadensis L.) roots powder from three commercial suppliers. J Agric Food Chem. 2003; 51(25):7352-7358.
  30. Mikkelsen SL, Ash KO. Adulterants causing false negatives in illicit drug testing. Clin Chem. 1988;34(11):2333-2336.
  31. AuthenTechnologies, Richmond CA. Case Study 1401: Fake Goldenseal is a Yellow Weed. Available at: http://www.authentechnologies.com/resources/case-studies/case-study-1401-fake-goldenseal/. Accessed July 17, 2015.
  32. Brinckmann J. Medicinal Plants and Extracts. Marketing News Service Quarterly. Dec. 2011. International Trade Centre. Available at: http://www.intracen.org/uploadedFiles/intracenorg/Content/Exporters/Market_Data_and_Information/Market_information/Market_Insider/Medicinal_plants/Medicinal%20Plants%20December%202011.pdf. Accessed August 13, 2015.
  33. Brown PN, Roman MC. Determination of hydrastine and berberine in goldenseal raw materials, extracts, and dietary supplements by high-performance liquid chromatography with UV: collaborative study, J AOAC Int. 2008;91(4):694–701.
  34. Avula B, Wang YH, Khan IA. Quantitative determination of alkaloids from the roots of Hydrastis Canadensis L. and dietary supplements using ultra-performance liquid chromatography with UV detection. J AOAC Int. 2012;95(5):1398-1405.
  35. Gardner Z, McGuffin M, eds. American Herbal Products Association’s Botanical Safety Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2013:155-159.
  36. Teschke R, Glass X, Schulze J. Herbal hepatotoxicity by Greater Celandine (Chelidonium majus): Causality assessment of 22 spontaneous reports. RTP. 2011: 61(i3):282-291.
  37. Official Method 2008.04-2008, Hydrastine and berberine in goldenseal raw materials, extracts and dietary supplements. Official Methods of Analysis of AOAC International, 19th ed. Gaithersuburg, MD: AOAC International; 2012.
  38. Weber HA, Zart, MK, Hodges AE, et al. Method validation for determination of alkaloid content in goldenseal root powder. 2002; J AOAC Int 86:476.
  39. Kamath S, Skeels M, Pai A. Significant differences in the alkaloid content of Coptis Chinensis (Huanglian), from its related American species. Chinese Medicine. 2009;4:17.
  40. Tims MC. The chemical ecology of Hydrastis Canadensis L. (Ranunculaceae): Effects of root isoquinoline alkaloids on the Hydrastis endophyte, Fusarium oxysporum. 2006. Available at: http://drum.lib.umd.edu/handle/1903/4052. Accessed July 17, 2015.
  41. Govindan M, Govindan G. A convenient method for the determination of the quality of goldenseal. Fitoterapia. 2000;71(3):232-235.
  42. Upton R. American Herbal Pharmacopoeia and Therapeutic Compendium: Goldenseal root. Hydrastis Canadensis. Santa Cruz, CA: American Herbal Pharmacopoeia. 2001.
  43. Van Berkel GJ, Tomkins BA, Kertesz V. Thin-layer chromatography/desorption electrospray ionization mass spectrometry: investigation of goldenseal alkaloids. Anal Chem. 2007;79(7):2778-2789.
  44. The European Directorate for the Quality of Medicines & HealthCare. European Pharmacopoeia (EP 8.7). Hydrastis rhizoma. Strasbourg, France: Council of Europe; 2015.2963.
  45. United States Pharmacopeial Convention. Goldenseal. In: USP 39-NF 34. Rockville, MD: United States Pharmacopeial Convention. 2016.
  46. Sturm S, Stuppner H. Analysis of isoquinoline alkaloids in medicinal plants by capillary electrophoresis—mass spectrometry. Electrophoresis. 1998;19(16‐17): 3026-3032.
  47. Chadwick LR, Wu CD, Kinghorn AD. Isolation of alkaloids from goldenseal (Hydrastis Canadensis rhizomes) using pH-zone-refining countercurrent chromatography. J Liq Chromatogr Rel Technol. 2001; 2445-2453;24(16):2445-2453.
  48. Bell SE, Bourguignon ESO, Dennis AC, Fields JA, McGarvey JJ, Seddon KR. Identification of dyes on ancient Chinese paper samples using the subtracted shifted Raman spectroscopy method. Anal Chem. 2000;72:234-239.
  49. Kim JS, Tanaka H, Shoyama Y. Immunoquantitative analysis for berberine and its related compounds using monoclonal antibodies in herbal medicines. Analyst. 2003;129(1):87-91.

Bulletin on Adulteration of Bilberry (Vaccinium myrtillus) Extracts

Goal:

The goal of this bulletin is to provide timely information and/or updates on issues of adulteration of bilberry extract to the international herbal industry and extended natural products community in general.

1 General Information

1.1 Common name: Bilberry3

1.2 Other common names:

English: European blueberry, whortleberry, huckleberry4

Chinese: Hei guo yue ju (黑果越桔)

French: Myrtille, ambroche, ambreselle, brimbelle, gueule-noire, raisin des bois, vigne des montagnes

German: Heidelbeere, Blaubeere, Schwarzbeere, Waldbeere, Bickbeere, Moosbeere

Italian: Mirtillo, ampulette, asaire, bagole, baggiole, cesarelle, giasine, lambrune, mirtillo nero, murucule

Spanish: Arándano azul, mirtilo

1.3 Accepted Latin binomial: Vaccinium myrtillus L.5,6

1.4 Synonyms: Vaccinium myrtillus var. oreophilum (Rydb.) Dorn, Vaccinium myrtillus subsp. oreophilum (Rydb.) Á. Löve, D. Löve & B.M. Kapoor, Vaccinium oreophilum Rydb.5

1.5 Botanical family: Ericaceae

1.6 Plant part and form: Bilberry extracts are made from fresh bilberry fruit.1 The extracts are often standardized to 25% anthocyanidins or 36% anthocyanins. Products that claim these levels of compounds may in actuality contain the same amount as the differences are most often due to different quantitative values obtained from using different analytical techniques. In the case of bilberry, high-performance liquid chromatography (HPLC) provides a lower quantitative value than ultraviolet-visible spectrophotometry (UV/Vis).7 Also found on the market are bilberry leaf extracts, or combinations of bilberry fruit and leaf extracts. Extracts made entirely from bilberry leaves and properly labeled as such are not within the scope of this document.

1.7 General use(s): The indications for bilberry fruit include the symptomatic treatment of dysmenorrhea associated with premenstrual syndrome, circulatory disorders in patients with capillary leakage or peripheral vascular insufficiency, and ophthalmic disorders.1,4,8 In addition, bilberry fruit is used topically for mild inflammations of the oral mucosa.4,8


2 Market

2.1 Importance in the trade: In the United States, bilberry was among the top 20 herbal supplements between 2007 and 2012 in the food, drug and mass market with annual sales above US $1.4 million in this channel.9-13 The market volume has been fairly steady in recent years (D. Stanek oral communication, January 23, 2015).

2.2 Supply sources: Commercial bilberries are sourced mainly from Scandinavian and Eastern European countries. The World Blueberry Acreage & Production report lists Poland as the major producer of bilberry, followed by Russia, Ukraine and Scandinavia. Commercial bilberry for the production of bilberry extracts is sourced mainly from Eastern European (Lithuania, Romania, Poland, Russia and Ukraine) and Scandinavian (Sweden, Finland, Norway) countries, but also from France, Italy, and the Netherlands. (D. Stanek oral communication, January 23, 2015; E. M. Martinelli e-mail, November 16, 2015)

2.3 Raw material forms: Bilberry extracts are prepared from fresh berries that are frozen and then extracted with aqueous ethanol or aqueous methanol, and further concentrated according to the manufacturer’s proprietary processes. Generally, the extract yield is approximately 100 times lower than the initial weight of raw material, i.e., 1 kg of fresh bilberry will provide ca. 10 grams of bilberry dry extract (D. Stanek oral communication, January 23, 2015). Dry extract materials using other manufacturing processes are also available.

2.4 Market dynamics: Tracking the bilberry harvest volume is difficult as the fruit is generally harvested by local people (i.e., wildcrafted) who then sell the fruit to brokers. A report from the North American Blueberry Council indicates that the total harvest for wild Vaccinium species (mostly bilberry, but other Vaccinium species, e.g., bog bilberry [V. uliginosum], are collected as well) in Europe was 11,340 metric tons (25 million lbs.) in 2008, 7,710 metric tons (17 million lbs.) in 2010, and 19,500 metric tons (43 million lbs.) in 2012.14

For 2012, the harvest in Poland was around 10,000 metric tons, but the harvest was mainly destined for the domestic market for confectionary and baked goods. Russia, Ukraine, and Scandinavia provided at least an additional 6,000 metric tons to the overall harvest.14 According to the report, the harvest in 2012 was particularly strong despite unfavorable weather conditions; since the economy was depressed in European countries, many people harvested wild blueberries for additional revenue.


3 Adulteration

3.1 Known adulterants: Materials that are used to adulterate bilberry extracts typically have an intensive dark blue color, such as anthocyanidin-containing extracts or red food coloring such as amaranth dye (FD&C Red 2, E 123). Anthocyanidin-rich extracts known to be used as substitute for bilberry include those from bog bilberry (Vaccinium uliginosum), lingonberry (V. vitis-idaea), blueberry species (V. angustifolium, V. corymbosum, V. floribundum), cranberry (V. oxycoccos and V. macrocarpon), raspberries (Rubus spp., Rosaceae), wild cherry (Prunus avium, Rosaceae), black chokeberry (Aronia melanocarpa, Rosaceae), European elder (Sambucus nigra, Adoxaceae) berry, black soybean (Glycine max, Fabaceae) hull, black rice (Oryza sativa, Poaceae), and mulberry species (Morus australis, M. nigra, Moraceae).2,15-18

The common names “blueberry” and “wild blueberry” have different meanings depending on the geographical location. In the US dietary supplement trade, the name “blueberry” is restricted to three species, Vaccinium angustifolium, V. corymbosum, and V. pallidum.3 In Europe, V. myrtillus is often called blueberry, though bilberry is the English word which refers to this species in the trade.3 The hybrid cultivated blueberries from which the majority of the commercial food supply is derived are generally called blueberries. North American wild blueberry, common blueberry, common lowbush blueberry, low sweet blueberry, and lowbush blueberry refer to V. angustifolium which grows in the Northeastern U.S. and is commercially harvested in its habitat. Velvet leaf blueberry (V. myrtilloides) is also traded as “wild blueberry,” and is mostly wild-harvested in the Canadian maritime provinces. It is safe to assume that “wild blueberry” in a commercial sense refers to both V. angustifolium and V. myrtilloides (Steven Foster, e-mail, July 1, 2015).

3.2 Sources of information confirming adulteration: There have been a number of publications on bilberry adulteration, such as the reviews by Foster and Blumenthal,2 Giacomelli et al.,16 Upton et al.,1 the presentation by Pace et al.,19 and the doctoral thesis by Primetta.20 Foster and Blumenthal distinguish between the deliberate adulteration of bilberry extracts by addition of extracts from anthocyanin-rich sources such as blueberry, cranberry, European elder, sweet cherry, and others, and the adulteration occurring in the markets in China, where extracts of lingonberry and bog bilberry are wild-harvested and offered as “homemade Chinese bilberry” and “Chinese domestic bilberry” extracts at prices as low as $10/kg.2 This is in contrast to the much more expensive authentic bilberry extract (see section 3.3 below). Two additional studies regarding adulteration of commercial bilberry extracts were published in 2013 and 2014.15,21 The investigation into the quality of 20 dietary supplements purchased in a store or over the Internet in Japan by ultra-high-performance liquid chromatography (UHPLC) with detection by visible light at 535 nm provided evidence for adulteration in one sample. The product in question was labeled to contain a mixture of bilberry and black currant (Ribes nigrum, Grossulariaceae) extracts, but instead consisted entirely of black currant.21 Gardana et al. analyzed 26 commercial bilberry materials including 14 bulk extracts, six food supplements, and six juices by UV/Vis spectrophotometry and by UHPLC using a photodiode array detector (DAD). The samples were purchased either directly from the supplier (bulk extracts), or from herbal shops and local markets in Italy. The authors found an admixture of black mulberry in five samples (two extracts, three food supplements), and substitution of bilberry with chokeberry in two extracts and with a material tentatively identified as blackberry (Rubus spp.) in one extract. One food supplement did not contain any anthocyanins at all. Five of the juices were consistent with products made from bilberry fruit, while one juice did not contain measurable amounts of anthocyanins.15

3.3 Accidental or intentional adulteration: The limited supply and high commodity prices of bilberry raw materials have created an incentive for economically-motivated adulteration. In 2015 authentic bilberry extracts sold for a price of US $600-800/kg extract (D. Stanek oral communication, January 23, 2015). More easily accessible anthocyanin-containing fruit species can be collected in larger amounts than bilberry in a comparatively short time since many of these are readily available from cultivated rather than more expensive wild sources. The fruit from these other species can be made into extracts at a significantly lower cost than bilberry and can be priced below bilberry market rates while producing a profit for the producer/seller.

3.4 Frequency of occurrence: There are very little data on the extent of adulteration of commercial bilberry extracts and dietary supplements. A presentation by Pace et al. suggested that “adulteration of bilberry is rampant”;19 Roberto Pace, PhD, Director of Quality Control at Indena S.p.A. (Milan, Italy), the world’s leading marketer of bilberry extract whose use has been confirmed in clinical trials, commented that “bilberry is one of the most economically adulterated ingredients of the health food market” (R. Pace oral communication, November 5, 2015). As noted above, one study included results of 20 commercial products purchased in Japan, with only 13 of the products labeled to contain bilberry. Of these 13 products, one was found to be entirely composed of black currant, while the remainder did contain authentic bilberry.21 Another study looked at bilberry extracts from different manufacturers and supplements purchased on local markets in Italy. The results indicated that six out of 14 extracts and four out of six supplements were adulterated.15 Lee analyzed 15 commercial bilberry supplements purchased in the states of Washington and Idaho in the United States. Five products contained authentic bilberry material, and two samples could not be evaluated because they were composed of a mixture of anthocyanin-containing fruits, including bilberry. The remaining eight products were found to be adulterated.18 Based on the limited published data available, it is not possible to come to any conclusions about the frequency of bilberry adulteration, but it is accurate to say that it is not uncommon.

3.5 Possible safety/therapeutic issues: Most of the known adulterants of bilberry have a long-standing history of safe use in food and therefore do not represent a safety concern. However, adulteration of bilberry extracts with amaranth dye is of possible safety concern. Amaranth dye has been prohibited for use by the US Food and Drug Administration (FDA) since 1976 due to concerns about carcinogenicity, which are mainly based on two controversial studies in rats.22,23 The use of amaranth dye is still permitted in Europe but is limited to 0.15 mg/kg per day.24 Most botanical adulterants are cultivated plants and might be potentially contaminated by pesticides, largely used in the growing of berries. Conversely, pesticides are not an issue with wild-harvested bilberry.

3.6 Analytical methods to detect adulteration: The most suitable way to authenticate bilberry extracts and detect adulteration is by chemical analysis based on the specific anthocyanin fingerprint using either high-performance thin layer chromatography (HPTLC) or high-performance liquid chromatography (HPLC) with ultraviolet/visible (UV/Vis) and/or mass spectrometric (MS) detection. The monograph of the United States Pharmacopeia (USP)26 recommends use of HPLC, while that of the American Herbal Pharmacopoeia (AHP)1 and European Pharmacopoeia (EP)27 utilize the UV/Vis method after adequate identification tests have been performedThe use of UV/Vis spectrophotometry alone will allow measurement of total anthocyanins in bilberry extracts, but is not specific enough as an identity test. It can be applied as a quantitative tool only after the identity of the raw material has been assured. A comprehensive evaluation of 39 publicly available methods for the authentication and detection of adulterants in bilberry extracts, the Bilberry Extract Laboratory Guidance Document, is available through the ABC-AHP-NCNPR Botanical Adulterants Program.25

3.7 Perspectives: Don Stanek, US Sales Director at Linnea Inc., a European producer of bilberry extract, commented that adulteration of bilberry extracts is likely to persist, since the authentic material is so expensive (oral communication, January 23, 2015). Furthermore, explains Giovanni Appendino, PhD, professor of pharmaceutical sciences at the University ofEastern Piedmont (Novara, Italy) and consultant to Indena, the leading producer of bilberry extract, the price of the berries is subjected to significant variations due to the effect of climate on the labor-intensive harvest (e-mail, July 20, 2015).


4 Conclusions:
The adulteration of bilberry extracts continues to afflict the natural products industry. Since the raw material is harvested in the wild, the control of the supply chain is more challenging and adequate testing of the incoming raw material is crucial. Test methods outlined, e.g., in the USP,26 the EP,27 or in the AHP1 are able to detect adulteration of bilberry extracts and should be in place in every quality control laboratory to prevent manufacturers of bilberry extract products from becoming victims of companies providing fraudulent ingredients.


5 References

  1. Upton R, Graff A, Petrone C, Swisher D. American Herbal Pharmacopoeia and Therapeutic Compendium: Bilberry Fruit. Vaccinium myrtillus L.: Standards of Analysis, Quality Control and Therapeutics. Scotts Valley, CA: American Herbal Pharmacopoeia; 2001.
  2. Foster S, Blumenthal. The adulteration of commercial bilberry extracts. HerbalGram. 2012;96:63-74. Available at: http://cms.herbalgram.org/herbalgram/issue96/hg96-feat-bilberry.html. Accessed February 14, 2015.
  3. McGuffin M, Kartesz JT, Leung AY, Tucker AO. American Herbal Products Association’s Herbs of Commerce. 2nd ed. Silver Spring, MD: American Herbal Products Association; 2000.
  4. Blumenthal M, Goldberg A, Brinckmann J (eds). Herbal Medicine: Expanded Commission E Monographs. Austin, TX: American Botanical Council; Newton, MA: Integrative Medicine Communications; 2000:16-21.
  5. The Plant List. Version 1.1 (September 2013). Available at: http://www.theplantlist.org. Accessed February 24, 2015.
  6. Tropicos.org. Missouri Botanical Garden. Available at: http://www.tropicos.org. Accessed February 24, 2015.
  7. Artaria C, Pace R, Maramaldi G, Appendino G. Different brands of bilberry extract: A comparison of selected components. Nutrafoods. 2007;6:13-18.
  8. World Health Organization: WHO monographs on selected plants, Volume 4. Fructus Myrtilli. WHO Press 2009;210-225.
  9. Cavaliere C, Rea P, Blumenthal M. Herbal supplement sales in United States show growth in all channels.HerbalGram. 2008;78:60-63. Available at: http://cms.herbalgram.org/herbalgram/issue78/article3263.html. Accessed February 14, 2015.
  10. Cavaliere C, Rea P, Lynch ME, Blumenthal M. Herbal supplement sales experience slight increase in 2008.HerbalGram. 2009;82:58-61. Available at: http://cms.herbalgram.org/herbalgram/issue82/article3400.html. Accessed February 14, 2015.
  11. Cavaliere C, Rea P, Lynch ME, Blumenthal M. Herbal supplement sales rise in all channels in 2009. HerbalGram.2010;86:62-65. Available at: http://cms.herbalgram.org/herbalgram/issue86/article3530.html. Accessed February 14, 2015.
  12. Blumenthal M, Lindstrom A, Lynch ME, Rea P. Herbs sales continue growth – up 3.3% in 2010. HerbalGram.2011;90:64-67. Available at: http://cms.herbalgram.org/herbalgram/issue90/MarketReport.html. Accessed February 14, 2015.
  13. Blumenthal M, Lindstrom A, Ooyen C, Lynch ME. Herb supplement sales increase 4.5% in 2011. HerbalGram.2012;95:60-64. Available at: http://cms.herbalgram.org/herbalgram/issue95/hg95-mktrpt.html. Accessed February 14, 2015.
  14. Brazelton C. 2012 World Blueberry Acreage and Production Report. North American Blueberry Council. 2013.
  15. Gardana C, Ciappellano S, Marinoni L, Fachechi C, Simonetti P. Bilberry adulteration: identification and chemical profiling of anthocyanins by different analytical methods. J Agric Food Chem. 2014;62(45):10998-11004.
  16. Giacomelli L, Appendino G, Franceschi F, Togni S, Pace R. Omne Ignotum pro Magnifico: characterization of commercial Bilberry extracts to fight adulteration. Eur Rev Med Pharmacol Sci. 2014;18(24):3948-3953.
  17. Filippini R, Piovan A, Caniato R. Substitution of Vaccinium myrtillus L. for Aronia melanocarpa (Michx.) Elliott in acommercial batch. Plant Biosyst. 2011;145(1):175-181.
  18. Lee J. Anthocyanin analyses of Vaccinium fruit dietary supplements. Food Sci Nutr. 2016. doi: 10.1002/fsn3.339.
  19. Pace R, Morazzoni P, Appendino G. Omne ignotum pro magnifico: Getting bilberry out of the adulteration swamp. Talk presented at: 9th Oxford International Conference on the Science of Botanicals; April 14, 2010; Oxford, MS.
  20. Primetta A. Phenolic compounds in the berries of the selected Vaccinium species – the potential for authenticity analyses. PhD thesis. Kuopio, Finland: University of Eastern Finland; 2014.
  21. Yamamoto M, Yamaura K, Ishiwatari M, et al. Degradation index for quality evaluation of commercial dietary supplements of bilberry extract. J Food Sci. 2013;78:S477–S483.
  22. Andrianova MM. Carcinogenous properties of red food pigments – amaranth, SX purple and 4R purple, Vop. Pitan. 1970;29:61-65.
  23. Baigusheva MM. Carcinogenic properties of the amaranth paste, Vop. Pitan. 1968:27:46-50.
  24. European Food Safety Authority. Scientific Opinion on the re-evaluation of Amaranth (E 123) as a food additive. EFSA Journal. 2010;8(7):1649.
  25. Gafner S. Bilberry Extract Adulteration Laboratory Guidance Document. ABC-AHP-NCNPR Botanical Adulterants Program, Austin, TX. 2015. http://cms.herbalgram.org/BAP/LGD/BilberryLabGuidanceDocument.html. Accessed August 25, 2015.
  26. United States Pharmacopeial Convention. Powdered Bilberry Extract. In: USP 37-NF 32. Rockville, MD: United States Pharmacopeial Convention. 2014.
  27. The European Directorate for the Quality of Medicines. European Pharmacopoeia (EP 7.5). Myrtilli fructus recentis extractum siccum raffinatum et normatum. Strasbourg, France: Council of Europe; 2012:1130-1132.