CHICAGO – Results of a prospective clinical trial in 100 men with metastatic castration-resistant prostate cancer (mCRPC) showed that black men were more likely to have a decline in prostate-specific antigen (PSA) and a longer median time to PSA rise in response to treatment with abiraterone (Zytiga) than white men receiving the same treatment (16.8 vs. 11.5 months).

The findings support earlier evidence indicating a stronger response to abiraterone among African Americans compared with Caucasians and suggest that at least some of the observed racial disparities in prostate cancer outcomes could be explained by genetic differences, according to lead study author Daniel George, MD, from Duke University in Durham, N.C.

In this video interview from the annual meeting of the American Society of Clinical Oncology, Dr. George discusses the study findings, as well as issues surrounding the problems of recruiting African Americans for clinical trials and ensuring access to the standard of advanced prostate cancer care for all patients.

Dr. George disclosed consulting or advisory roles and research funding from numerous pharmaceutical companies.

CHICAGO – Results of a prospective clinical trial in 100 men with metastatic castration-resistant prostate cancer (mCRPC) showed that black men were more likely to have a decline in prostate-specific antigen (PSA) and a longer median time to PSA rise in response to treatment with abiraterone (Zytiga) than white men receiving the same treatment (16.8 vs. 11.5 months).

The findings support earlier evidence indicating a stronger response to abiraterone among African Americans compared with Caucasians and suggest that at least some of the observed racial disparities in prostate cancer outcomes could be explained by genetic differences, according to lead study author Daniel George, MD, from Duke University in Durham, N.C.

In this video interview from the annual meeting of the American Society of Clinical Oncology, Dr. George discusses the study findings, as well as issues surrounding the problems of recruiting African Americans for clinical trials and ensuring access to the standard of advanced prostate cancer care for all patients.

Dr. George disclosed consulting or advisory roles and research funding from numerous pharmaceutical companies.

CHICAGO – Results of a prospective clinical trial in 100 men with metastatic castration-resistant prostate cancer (mCRPC) showed that black men were more likely to have a decline in prostate-specific antigen (PSA) and a longer median time to PSA rise in response to treatment with abiraterone (Zytiga) than white men receiving the same treatment (16.8 vs. 11.5 months).

The findings support earlier evidence indicating a stronger response to abiraterone among African Americans compared with Caucasians and suggest that at least some of the observed racial disparities in prostate cancer outcomes could be explained by genetic differences, according to lead study author Daniel George, MD, from Duke University in Durham, N.C.

In this video interview from the annual meeting of the American Society of Clinical Oncology, Dr. George discusses the study findings, as well as issues surrounding the problems of recruiting African Americans for clinical trials and ensuring access to the standard of advanced prostate cancer care for all patients.

Dr. George disclosed consulting or advisory roles and research funding from numerous pharmaceutical companies.

CHICAGO – Women with head and neck cancer less commonly receive intensive chemotherapy (35% vs. 46%) and radiation therapy (60% vs. 70%) than do their male counterparts, finds an analysis of 223 female patients and 661 male patients with stage II-IVB disease treated at Kaiser Permanente Northern California. And this apparent undertreatment may be compromising survival for women, as their ratio of cancer deaths to other deaths is nearly twice that of men (adjusted relative hazard ratio, 1.92; 95% CI, 1.07-3.43).

In this video interview from the annual meeting of the American Society of Clinical Oncology, senior study author Jed A. Katzel, MD, of Kaiser Permanente in Santa Clara, Calif., described the new statistical approach used to assess outcomes and discussed ongoing research to pin down the reasons for the apparent treatment disparities, including patient preferences and the influences of tumor site and HPV status.

Dr. Katzel reported no financial disclosures.

CHICAGO – Women with head and neck cancer less commonly receive intensive chemotherapy (35% vs. 46%) and radiation therapy (60% vs. 70%) than do their male counterparts, finds an analysis of 223 female patients and 661 male patients with stage II-IVB disease treated at Kaiser Permanente Northern California. And this apparent undertreatment may be compromising survival for women, as their ratio of cancer deaths to other deaths is nearly twice that of men (adjusted relative hazard ratio, 1.92; 95% CI, 1.07-3.43).

In this video interview from the annual meeting of the American Society of Clinical Oncology, senior study author Jed A. Katzel, MD, of Kaiser Permanente in Santa Clara, Calif., described the new statistical approach used to assess outcomes and discussed ongoing research to pin down the reasons for the apparent treatment disparities, including patient preferences and the influences of tumor site and HPV status.

Dr. Katzel reported no financial disclosures.

CHICAGO – Women with head and neck cancer less commonly receive intensive chemotherapy (35% vs. 46%) and radiation therapy (60% vs. 70%) than do their male counterparts, finds an analysis of 223 female patients and 661 male patients with stage II-IVB disease treated at Kaiser Permanente Northern California. And this apparent undertreatment may be compromising survival for women, as their ratio of cancer deaths to other deaths is nearly twice that of men (adjusted relative hazard ratio, 1.92; 95% CI, 1.07-3.43).

In this video interview from the annual meeting of the American Society of Clinical Oncology, senior study author Jed A. Katzel, MD, of Kaiser Permanente in Santa Clara, Calif., described the new statistical approach used to assess outcomes and discussed ongoing research to pin down the reasons for the apparent treatment disparities, including patient preferences and the influences of tumor site and HPV status.

Dr. Katzel reported no financial disclosures.

NIH researchers tested the common wisdom that opioids act only on the same surface receptors as endogenous opioids. They discovered that opioids, such as morphine and oxycodone, bind to receptors inside neurons—which are not the targets of naturally occurring opioids. The difference in the actions could help guide the design of pain relievers that do not produce addiction or other adverse opioid-related effects.

The researchers used a new type of antibody biosensor—a nanobody—that generates a fluorescent signal when certain proteins are activated. The signal allowed researchers to track chemicals as they move through cells and responded to stimuli.

The first discovery was that the opioid receptors were activated not only on the surface, but also in the endosome, where the mu-receptor remained activated over several minutes. The researchers also found that there are large differences across a range of opioid drugs in how strongly they induce receptor activation in the endosome. Yet another discovery was that the opioid drugs uniquely induce rapid nanobody signaling, within tens of seconds, in the Golgi apparatus. Therapeutic opioids also uniquely activated mu-opioid receptors in Golgi outposts, in the long, branched structures of neurons.

Based on those findings, the researchers hypothesize that current medically used opioids distort the normal time and spatial sequence of mu-opioid receptor activating and signaling. That distortion may provide the mechanistic link, they say, that explains the undesired adverse effects of opioid medicines.

NIH researchers tested the common wisdom that opioids act only on the same surface receptors as endogenous opioids. They discovered that opioids, such as morphine and oxycodone, bind to receptors inside neurons—which are not the targets of naturally occurring opioids. The difference in the actions could help guide the design of pain relievers that do not produce addiction or other adverse opioid-related effects.

The researchers used a new type of antibody biosensor—a nanobody—that generates a fluorescent signal when certain proteins are activated. The signal allowed researchers to track chemicals as they move through cells and responded to stimuli.

The first discovery was that the opioid receptors were activated not only on the surface, but also in the endosome, where the mu-receptor remained activated over several minutes. The researchers also found that there are large differences across a range of opioid drugs in how strongly they induce receptor activation in the endosome. Yet another discovery was that the opioid drugs uniquely induce rapid nanobody signaling, within tens of seconds, in the Golgi apparatus. Therapeutic opioids also uniquely activated mu-opioid receptors in Golgi outposts, in the long, branched structures of neurons.

Based on those findings, the researchers hypothesize that current medically used opioids distort the normal time and spatial sequence of mu-opioid receptor activating and signaling. That distortion may provide the mechanistic link, they say, that explains the undesired adverse effects of opioid medicines.

NIH researchers tested the common wisdom that opioids act only on the same surface receptors as endogenous opioids. They discovered that opioids, such as morphine and oxycodone, bind to receptors inside neurons—which are not the targets of naturally occurring opioids. The difference in the actions could help guide the design of pain relievers that do not produce addiction or other adverse opioid-related effects.

The researchers used a new type of antibody biosensor—a nanobody—that generates a fluorescent signal when certain proteins are activated. The signal allowed researchers to track chemicals as they move through cells and responded to stimuli.

The first discovery was that the opioid receptors were activated not only on the surface, but also in the endosome, where the mu-receptor remained activated over several minutes. The researchers also found that there are large differences across a range of opioid drugs in how strongly they induce receptor activation in the endosome. Yet another discovery was that the opioid drugs uniquely induce rapid nanobody signaling, within tens of seconds, in the Golgi apparatus. Therapeutic opioids also uniquely activated mu-opioid receptors in Golgi outposts, in the long, branched structures of neurons.

Based on those findings, the researchers hypothesize that current medically used opioids distort the normal time and spatial sequence of mu-opioid receptor activating and signaling. That distortion may provide the mechanistic link, they say, that explains the undesired adverse effects of opioid medicines.

CMV infection

A small retrospective study of 23 transplant patients has confirmed that CMV hyperimmune globulin (Cytotect^®CP) is a safe and effective salvage therapy for patients with cytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplant (allo-HCT).

Cytotect^®CP used as salvage therapy resulted in a 78% overall response rate and 70% of all patients cleared CMV infection, according to investigators.

They observed no clinically significant adverse events.

CMV is a major factor contributing to high mortality rates in allo-HCT patients.

And because Cytotect^®CP is less toxic than commonly used treatments for CMV infection, investigators suggested that it be used prophylactically in patients known to have a predisposition to CMV infection.

They reported their findings in the journal Bone Marrow Transplantation.

Patient characteristics and methods

All 23 patients transplanted at 8 centers in France were CMV seropositive at the time of transplant, and 70% received the transplant from a CMV serostatus negative donor.

Recipient positivity and donor negativity, the investigators indicated, is a risk factor for developing recurrent CMV infection after allo-HCT.

The patients’ median age was 53, 11 were male and 12 female.

Five patients (22%) received a haploidentical transplant and 14 (61%) from an unrelated donor, which the investigators pointed out is also a known risk factor for developing recurrent CMV infection.

Thirteen (57%) were in complete remission from their underlying disease, 4 (17%) in partial remission, 1 (4%) had stable disease, and 5 (22%) were in relapse or had progressive disease.

Most (83%) had a peripheral blood transplant, 15 (65%) had a reduced intensity conditioning regimen, and 16 (70%) had antithymocyte globulin as part of their conditioning regimen.

All patients received valacyclovir as antiviral prophylaxis prior to receiving Cytotect^®CP. The investigators mentioned in the paper that valacyclovir has not been proven to be effective in treating CMV.

They noted that other CMV treatments, such as ganciclovir, foscavir, and dicofovir, cause high levels of toxicity, frequently leading to treatment discontinuation.

Seventeen patients (74%) had a history of graft-versus-host disease (GVHD), and 11 (49%) had active GVHD at the time CMV hyperimmune globulin was administered.

Investigators used quantitative polymerase chain reaction (PCR) to quantify CMV viral load in the blood.

Treatment could begin when patients’ viral load was greater than 3-3.5 log UI/mL, according to the Francophone Society of Bone Marrow Transplantation and Cellular therapy.

Three patients received Cytotect^®CP at a prophylaxis dose (200 U/kg/week) to prevent CMV recurrences and 20 as preemptive therapy (400 U/kg on days 1, 4, 8 then 200 U/kg on days 12and 16).

Seven patients (30%) received Cytotect^®CP as monotherapy, 5 (22%) in combination with ganciclovir, 5 (22%) in combination with foscavir, 2 (9%) in combination with ganciclovir and foscavir, and 4 (17%) with some other combination.

Investigators restricted their analysis to 100-day overall survival (OS), starting at the beginning of Cytotect^®CP treatment to death within 100 days, regardless of the cause of death.

Results

Eighteen patients (78%) responded to Cytotect®CP, and 16 of the responders converted to CMV-PCR negative.

Median time to achieve CMV-PCR response was 15 days (range, 3-51).

Four patients did not respond to therapy, and 1 patient had a non-evaluable response. The latter patient died 13 days after the introduction of Cytotect^®CP due to another infection.

Eight patients died within 100 days after initiation of Cytotect^®CP. Two deaths were related to CMV and 6 were unrelated.

Four patients who responded to Cytotect^®CP experienced CMV relapse between 9 and 49 days after their best response to therapy.

Five responders died within 100 days due to the following causes: GVHD (n = 2), other infection (n = 1), underlying disease (n = 1), and CMV-related causes (n = 1).

Two of the 4 nonresponders died of other infection (n = 1) and GVHD (n = 1).

Investigators estimated the 100-day OS from the start of Cytotect^®CP to be 69.6%. They observed no statistical difference (P=0.258) between those who responded (73.7%) and those who didn’t (50.0%).

The investigators believe that Cytotect^®CP is an alternative option for treatment of CMV infection because it avoids renal and bone marrow impairment and should be considered as prophylaxis in select patients.

They recommend a large prospective study be conducted to confirm safety and efficacy results of CMV hyperimmune globulin.

Cytotect^®CP is authorized in more than 15 countries for the prophylaxis of CMV infection in patients receiving immunosuppressive treatment, particularly transplant recipients.

In French transplant centers, according to the study authors, use of Cytotect^®CP  is limited to the salvage setting for recurrent or refractory CMV infections and sometimes in combination for CMV pneumonia.

Biotest, the commercializer of Cytotect®CP, provided a grant for this study. 

CMV infection

A small retrospective study of 23 transplant patients has confirmed that CMV hyperimmune globulin (Cytotect^®CP) is a safe and effective salvage therapy for patients with cytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplant (allo-HCT).

Cytotect^®CP used as salvage therapy resulted in a 78% overall response rate and 70% of all patients cleared CMV infection, according to investigators.

They observed no clinically significant adverse events.

CMV is a major factor contributing to high mortality rates in allo-HCT patients.

And because Cytotect^®CP is less toxic than commonly used treatments for CMV infection, investigators suggested that it be used prophylactically in patients known to have a predisposition to CMV infection.

They reported their findings in the journal Bone Marrow Transplantation.

Patient characteristics and methods

All 23 patients transplanted at 8 centers in France were CMV seropositive at the time of transplant, and 70% received the transplant from a CMV serostatus negative donor.

Recipient positivity and donor negativity, the investigators indicated, is a risk factor for developing recurrent CMV infection after allo-HCT.

The patients’ median age was 53, 11 were male and 12 female.

Five patients (22%) received a haploidentical transplant and 14 (61%) from an unrelated donor, which the investigators pointed out is also a known risk factor for developing recurrent CMV infection.

Thirteen (57%) were in complete remission from their underlying disease, 4 (17%) in partial remission, 1 (4%) had stable disease, and 5 (22%) were in relapse or had progressive disease.

Most (83%) had a peripheral blood transplant, 15 (65%) had a reduced intensity conditioning regimen, and 16 (70%) had antithymocyte globulin as part of their conditioning regimen.

All patients received valacyclovir as antiviral prophylaxis prior to receiving Cytotect^®CP. The investigators mentioned in the paper that valacyclovir has not been proven to be effective in treating CMV.

They noted that other CMV treatments, such as ganciclovir, foscavir, and dicofovir, cause high levels of toxicity, frequently leading to treatment discontinuation.

Seventeen patients (74%) had a history of graft-versus-host disease (GVHD), and 11 (49%) had active GVHD at the time CMV hyperimmune globulin was administered.

Investigators used quantitative polymerase chain reaction (PCR) to quantify CMV viral load in the blood.

Treatment could begin when patients’ viral load was greater than 3-3.5 log UI/mL, according to the Francophone Society of Bone Marrow Transplantation and Cellular therapy.

Three patients received Cytotect^®CP at a prophylaxis dose (200 U/kg/week) to prevent CMV recurrences and 20 as preemptive therapy (400 U/kg on days 1, 4, 8 then 200 U/kg on days 12and 16).

Seven patients (30%) received Cytotect^®CP as monotherapy, 5 (22%) in combination with ganciclovir, 5 (22%) in combination with foscavir, 2 (9%) in combination with ganciclovir and foscavir, and 4 (17%) with some other combination.

Investigators restricted their analysis to 100-day overall survival (OS), starting at the beginning of Cytotect^®CP treatment to death within 100 days, regardless of the cause of death.

Results

Eighteen patients (78%) responded to Cytotect®CP, and 16 of the responders converted to CMV-PCR negative.

Median time to achieve CMV-PCR response was 15 days (range, 3-51).

Four patients did not respond to therapy, and 1 patient had a non-evaluable response. The latter patient died 13 days after the introduction of Cytotect^®CP due to another infection.

Eight patients died within 100 days after initiation of Cytotect^®CP. Two deaths were related to CMV and 6 were unrelated.

Four patients who responded to Cytotect^®CP experienced CMV relapse between 9 and 49 days after their best response to therapy.

Five responders died within 100 days due to the following causes: GVHD (n = 2), other infection (n = 1), underlying disease (n = 1), and CMV-related causes (n = 1).

Two of the 4 nonresponders died of other infection (n = 1) and GVHD (n = 1).

Investigators estimated the 100-day OS from the start of Cytotect^®CP to be 69.6%. They observed no statistical difference (P=0.258) between those who responded (73.7%) and those who didn’t (50.0%).

The investigators believe that Cytotect^®CP is an alternative option for treatment of CMV infection because it avoids renal and bone marrow impairment and should be considered as prophylaxis in select patients.

They recommend a large prospective study be conducted to confirm safety and efficacy results of CMV hyperimmune globulin.

Cytotect^®CP is authorized in more than 15 countries for the prophylaxis of CMV infection in patients receiving immunosuppressive treatment, particularly transplant recipients.

In French transplant centers, according to the study authors, use of Cytotect^®CP  is limited to the salvage setting for recurrent or refractory CMV infections and sometimes in combination for CMV pneumonia.

Biotest, the commercializer of Cytotect®CP, provided a grant for this study. 

CMV infection

A small retrospective study of 23 transplant patients has confirmed that CMV hyperimmune globulin (Cytotect^®CP) is a safe and effective salvage therapy for patients with cytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplant (allo-HCT).

Cytotect^®CP used as salvage therapy resulted in a 78% overall response rate and 70% of all patients cleared CMV infection, according to investigators.

They observed no clinically significant adverse events.

CMV is a major factor contributing to high mortality rates in allo-HCT patients.

And because Cytotect^®CP is less toxic than commonly used treatments for CMV infection, investigators suggested that it be used prophylactically in patients known to have a predisposition to CMV infection.

They reported their findings in the journal Bone Marrow Transplantation.

Patient characteristics and methods

All 23 patients transplanted at 8 centers in France were CMV seropositive at the time of transplant, and 70% received the transplant from a CMV serostatus negative donor.

Recipient positivity and donor negativity, the investigators indicated, is a risk factor for developing recurrent CMV infection after allo-HCT.

The patients’ median age was 53, 11 were male and 12 female.

Five patients (22%) received a haploidentical transplant and 14 (61%) from an unrelated donor, which the investigators pointed out is also a known risk factor for developing recurrent CMV infection.

Thirteen (57%) were in complete remission from their underlying disease, 4 (17%) in partial remission, 1 (4%) had stable disease, and 5 (22%) were in relapse or had progressive disease.

Most (83%) had a peripheral blood transplant, 15 (65%) had a reduced intensity conditioning regimen, and 16 (70%) had antithymocyte globulin as part of their conditioning regimen.

All patients received valacyclovir as antiviral prophylaxis prior to receiving Cytotect^®CP. The investigators mentioned in the paper that valacyclovir has not been proven to be effective in treating CMV.

They noted that other CMV treatments, such as ganciclovir, foscavir, and dicofovir, cause high levels of toxicity, frequently leading to treatment discontinuation.

Seventeen patients (74%) had a history of graft-versus-host disease (GVHD), and 11 (49%) had active GVHD at the time CMV hyperimmune globulin was administered.

Investigators used quantitative polymerase chain reaction (PCR) to quantify CMV viral load in the blood.

Treatment could begin when patients’ viral load was greater than 3-3.5 log UI/mL, according to the Francophone Society of Bone Marrow Transplantation and Cellular therapy.

Three patients received Cytotect^®CP at a prophylaxis dose (200 U/kg/week) to prevent CMV recurrences and 20 as preemptive therapy (400 U/kg on days 1, 4, 8 then 200 U/kg on days 12and 16).

Seven patients (30%) received Cytotect^®CP as monotherapy, 5 (22%) in combination with ganciclovir, 5 (22%) in combination with foscavir, 2 (9%) in combination with ganciclovir and foscavir, and 4 (17%) with some other combination.

Investigators restricted their analysis to 100-day overall survival (OS), starting at the beginning of Cytotect^®CP treatment to death within 100 days, regardless of the cause of death.

Results

Eighteen patients (78%) responded to Cytotect®CP, and 16 of the responders converted to CMV-PCR negative.

Median time to achieve CMV-PCR response was 15 days (range, 3-51).

Four patients did not respond to therapy, and 1 patient had a non-evaluable response. The latter patient died 13 days after the introduction of Cytotect^®CP due to another infection.

Eight patients died within 100 days after initiation of Cytotect^®CP. Two deaths were related to CMV and 6 were unrelated.

Four patients who responded to Cytotect^®CP experienced CMV relapse between 9 and 49 days after their best response to therapy.

Five responders died within 100 days due to the following causes: GVHD (n = 2), other infection (n = 1), underlying disease (n = 1), and CMV-related causes (n = 1).

Two of the 4 nonresponders died of other infection (n = 1) and GVHD (n = 1).

Investigators estimated the 100-day OS from the start of Cytotect^®CP to be 69.6%. They observed no statistical difference (P=0.258) between those who responded (73.7%) and those who didn’t (50.0%).

The investigators believe that Cytotect^®CP is an alternative option for treatment of CMV infection because it avoids renal and bone marrow impairment and should be considered as prophylaxis in select patients.

They recommend a large prospective study be conducted to confirm safety and efficacy results of CMV hyperimmune globulin.

Cytotect^®CP is authorized in more than 15 countries for the prophylaxis of CMV infection in patients receiving immunosuppressive treatment, particularly transplant recipients.

In French transplant centers, according to the study authors, use of Cytotect^®CP  is limited to the salvage setting for recurrent or refractory CMV infections and sometimes in combination for CMV pneumonia.

Biotest, the commercializer of Cytotect®CP, provided a grant for this study. 

More than a third of American adults use complementary and alternative medicine.¹ Unfortunately, the public’s enthusiasm for herbal products is not always consistent with the scientific evidence supporting their use. In part one of this series, we discussed the studies that have been done on capsaicin, butterbur, green tea, and peppermint. In this installment, we outline the research on 5 additional remedies: turmeric/curcumin, which may be of benefit in ulcerative colitis; chamomile, which appears to offer relief to patients with anxiety; rosemary, which may help treat alopecia; as well as coffee and cocoa, which may have some cardiovascular benefits (TABLE).

Turmeric/curcumin

Overview

Turmeric (Curcuma longa), a relative of ginger, has been used for 4000 years to treat a variety of conditions.^2,3 Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric.³ Turmeric powder contains 5% curcumin, which is the main biologically active compound. Although it grows in many tropical locations, most turmeric is grown in India, where it is used as a main ingredient in curry. The roots and bulbs of turmeric that are used in medicine are generally boiled and dried, which results in a yellow powder.

Turmeric has been used in both Ayurvedic and Chinese medicine for its anti-inflammatory properties, in the treatment of digestive and liver problems, to fight infections, and to help heal skin diseases and wounds.^3-7

Functional GI disorders. A recent review noted that curcumin has been shown in several preclinical studies and uncontrolled clinical trials to have effects on gut inflammation, gut permeability, and the brain-gut axis, especially in functional GI disorders.⁷ A double-blind, placebo-controlled study from 1989 found that turmeric reduced symptoms of bloating and gas in subjects suffering from undifferentiated dyspepsia.⁸

Ulcerative colitis (UC). A 2012 Cochrane review noted that curcumin appears to be a safe and effective therapy for maintenance of remission in quiescent UC when given as adjunctive therapy along with mesalamine or sulfasalazine.⁹ In a 2015 randomized controlled trial (RCT), the addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects.¹⁰

Osteoarthritis (OA). Because of turmeric’s ability to reduce inflammation, it may help relieve OA pain.³ Clinical evidence is scant for the anti-arthritic efficacy of turmeric dietary supplements, although animal studies indicate that turmeric prevents inflammation through regulation of NF-kappaB-regulated genes that regulate the immune and inflammatory response.⁶ Inflammatory cell influx, joint levels of prostaglandin E2, and periarticular osteoclast formation were also inhibited by turmeric extract treatment.⁶

A 2013 review of turmeric for OA concluded that observational studies and in vitro results are promising for the use of curcumin for OA, but well-designed clinical studies were lacking and are needed to support the efficacy of curcumin in OA patients.¹¹ How­ever, in a 2014 randomized trial of 367 patients, turmeric appeared to be similar in efficacy to ibuprofen for the treatment of pain and disability in adults with knee OA.¹² The curcumin (turmeric) group also had fewer adverse effects.¹²

Cancer. There has been a great deal of research on turmeric’s anti-cancer properties, but clinical evidence is lacking. In vitro evidence, animal studies, and small clinical trials suggest that curcumin may help prevent or treat several types of cancers, but the overall evidence is poor. Nonetheless, curcumin and turmeric have been or are currently being evaluated for the treatment or prevention of prostate, liver, breast, skin, gynecologic, hematologic, pulmonary, thymic, bone, brain, and colon cancer.^13-18

Oral submucous fibrosis. A small randomized trial found improvement in oral function with curcumin lozenges, when compared to placebo, indicating that turmeric may hold promise as a treatment of oral submucous fibrosis.¹⁹

Uveitis. A small pilot study of 32 patients suggested that oral curcumin may be as effective as corticosteroids for uveitis.²⁰

Heart disease. Curcumin may have a cardiovascular protective role, as it has been shown to reduce atherosclerosis, but a reduction in myocardial infarction or stroke has not been documented.²¹

Alzheimer’s dementia. Animal studies have shown a reduction in amyloid plaque formation with curcumin.²²

Adverse effects (and precautions)

Turmeric in food is considered safe. A variety of animal and human studies have also indicated that curcumin is safe and well tolerated, even at very high doses.¹³ However, taking large amounts of turmeric for long periods of time could cause stomach upset and gastric ulcers. In addition, patients with gallstones or bile obstruction should use it with caution due to increased bile production.⁷

Because turmeric may lower blood sugar levels, patients with diabetes should monitor for hypoglycemia when using turmeric in combination with diabetic medications. Similarly, those with bleeding disorders taking blood thinners should use turmeric and curcumin with caution, because it can inhibit platelet aggregation.²³

Although it is safe to eat foods with turmeric during pregnancy, pregnant and breastfeeding women should not take turmeric supplements, as the safety of large doses in pregnancy is unknown.

The bottom line

Turmeric/curcumin has anti-inflammatory properties and may be useful as an adjunct for ulcerative colitis and to improve the symptoms of OA. It may also have anti-carcinogenic properties, although definitive data are lacking. Those with a history of gastrointestinal conditions such as gastric ulcer, patients taking blood thinners, and patients with diabetes who are prone to low blood sugar levels should use turmeric/curcumin with caution.

Overview

Chamomile, a member of the Asteraceae/Compositae family, is one of the oldest herbal medicines. It has been used for hay fever, inflammation, muscle spasms, menstrual disorders, insomnia, ulcers, wounds, gastrointestinal disorders, rheumatic pain, and hemorrhoids. Essential oils of chamomile are used extensively in cosmetics and aromatherapy. Many different preparations have been developed, the most popular being herbal tea.²⁴

A controlled clinical trial of chamomile extract suggested that it may have modest anxiolytic activity in patients with mild to moderate generalized anxiety disorder.

Individuals with a hypersensitivity to plants of the Asteraceae (Compositae) family such as ragweed (Ambrosia spp.), marigold flower (Calendula officinalis), and chrysanthemum (Chrysanthemum spp.) may show a similar reaction to chamomile.²⁵

Anxiety. A controlled clinical trial of chamomile extract for generalized anxiety disorder (GAD) suggested that it may have modest anxiolytic activity in patients with mild to moderate GAD.²⁶ Another randomized, double-blind, placebo-controlled trial found oral chamomile extract was efficacious and well-tolerated in patients experiencing mild to moderate GAD and may provide an alternative therapeutic anxiolytic for patients with mild GAD.²⁵ In addition to its anxiolytic activity, chamomile may also provide clinically meaningful antidepressant activity.²⁶

Insomnia. Chamomile may have some impact on sleep diary measures (total sleep time, sleep efficiency, sleep latency, wake after sleep onset, sleep quality, and number of awakenings) relative to placebo in adults with chronic primary insomnia, according to a small randomized, double-blind, placebo-controlled pilot trial involving 34 patients.²⁷ However, a systematic review found no statistically significant difference between any herbal medicine (including chamomile) and placebo, for clinical efficacy in patients with insomnia. A similar, or smaller, number of adverse events per person were reported with chamomile compared with placebo, suggesting safe use.²⁸

Infantile colic. A small prospective double-blind study on the use of chamomile-containing tea on infantile colic showed statistically significant symptom improvement in tea-treated infants. The study did note, however, that prolonged ingestion of herbal teas may lead to decreased milk intake.^29,30

Adverse effects

As noted earlier, a systematic review found that the number of adverse events per person reported with chamomile was comparable to the number associated with placebo, suggesting that it is safe.²⁸

The bottom line

Chamomile appears to be safe with minimal adverse effects and may be effective for the treatment of anxiety, insomnia, and infantile colic.

Rosemary

Overview

Rosemary, officially known as Rosmarinus officinalis, is a medicinal evergreen plant native to the Mediterranean area that appears to increase microcapillary perfusion.³¹

Topical rosemary oil may be useful in the treatment of alopecia, with minimal adverse effects.

Alopecia. A randomized double-blind controlled trial found that essential oils including rosemary oil (as well as thyme, lavender, and cedarwood) massaged into the scalp improved hair growth in almost half of patients with alopecia areata after 7 months.³² Another randomized trial comparing rosemary oil to minoxidil 2% for androgenetic alopecia showed a significant increase in hair count at the 6-month endpoint compared with the baseline, but no significant difference was found between the study groups regarding hair count either at Month 3 or Month 6 (P >.05). ³¹

Adverse effects

In the randomized trial described above comparing rosemary oil to minoxidil 2%, adverse effects appeared to be rare for topical rosemary oil. Scalp itching was more frequent in the minoxidil group.³¹

The bottom line

Topical rosemary oil may be useful in the treatment of alopecia with minimal adverse effects.

Overview

Coffee is one of the most widely used botanicals with approximately 3.5 billion cups of coffee consumed per day worldwide. It is a popular beverage because of its unique aromatic taste and its use as a central nervous system stimulant. The coffee tree (genus coffea) is found throughout Latin America, Africa, and eastern Asia. Two of the most common commercially grown species are Coffea arabica (Arabicas) and Coffea canephora (Robusta). Processing and roasting methods may differ and produce variations in flavor and aroma. The degree of roasting also affects the caffeine content.

Coffee consumption leads to increased alertness and can boost mental performance. Based on the literature and US Food and Drug Administration recommendations, four 8-oz cups of coffee (about 400 mg of caffeine) daily is an acceptable average amount of caffeine. More than 500 mg/d is considered excessive use of coffee.^33,34

Overall mortality. A 2008 study showed that regular coffee was not associated with increased or decreased mortality in both men and women.³⁵ However, more recent studies show an inverse relationship between mortality and coffee consumption.

Specifically, a 2014 meta-analysis found an inverse relationship between coffee and mortality.³⁶ A large prospective cohort study from 2015 that included 79,234 women and 76,704 men found that drinking coffee was inversely associated with overall mortality.³⁷ In this cohort study, an inverse association were observed for deaths from heart disease, respiratory disease, diabetes, and self-harm.³⁷ While mechanisms were not analyzed, coffee may reduce mortality risk by affecting inflammation, lung function, insulin sensitivity, and depression.

Cardiovascular disease. Coffee consumption may modestly reduce the risk of stroke, according to a prospective cohort study of 83,076 women from the Nurses’ Health Study who were followed for 24 years.³⁸ Reduced cardiovascular mortality was also found in a large prospective cohort study, as noted in the mortality discussion above.³⁷ A 2014 meta-analysis concluded that coffee consumption is inversely associated with cardiovascular mortality. Drinking 3 or 4 cups a day appears to be the amount that may decrease one’s risk of death when compared to those who do not drink coffee at all.³⁶

Liver disease. Friedrich et al performed a study involving 379 patients with end stage liver disease, and found that coffee consumption delayed the progression of disease in patients with both alcoholic liver disease and primary sclerosing cholangitis.³⁹ Coffee consumption also increased long-term survival after liver transplantation.³⁹ However, the study found that coffee did not have any effect on patients with chronic viral hepatitis.

In a 2016 meta-analysis, caffeinated coffee consumption reduced hepatic fibrosis of nonalcoholic fatty liver disease, although caffeine consumption did not reduce the prevalence of nonalcoholic fatty liver disease.⁴⁰ Another meta-analysis, including 16 studies, also found caffeine reduced the risk for hepatic fibrosis and cirrhosis.⁴¹

Depression. Based on 2 different systematic reviews and meta-analyses from 2016, coffee consumption appears to have a significant protective effect, decreasing the risk of developing depression.^40,42

Alzheimer’s disease/dementia. Coffee, tea, and caffeine consumption show promise in reducing the risk of cognitive decline and dementia. Individuals who consume one to 2 cups of coffee per day had a decreased incidence of mild cognitive impairment compared to non-drinkers.⁴³ A 2015 Japanese study also found an inverse association between coffee consumption and dementia among women, nonsmokers, and those who do not drink alcohol.⁴⁴ Most recently, a 2016 study, the Women’s Health Initiative Memory Study, looked at incident dementia rates in women >65 years of age with high vs low caffeine intake. Women with higher caffeine intake were less likely to develop dementia or any cognitive impairment compared with those consuming <64 mg/day.⁴⁵

Type 2 diabetes. A 2009 prospective cohort study, which included 40,011 participants followed for more than 10 years, found that drinking at least 3 cups of coffee or tea was associated with a lowered risk of type 2 diabetes.⁴⁶ A 2009 systematic review of 20 cohort studies showed that high intakes of coffee, decaffeinated coffee, and tea are associated with a reduced risk of diabetes.⁴⁷

A meta-analysis of 12 studies involving 832,956 participants found an inverse relationship between cutaneous melanoma and coffee consumption.

Melanoma. A meta-analysis of 12 studies involving 832,956 participants demon­strated an inverse relationship between cutaneous melanoma and coffee consumption.⁴⁷ The risk of melanoma decreased by 3% and 4% for one cup/day of total coffee and caffeinated coffee consumption, respectively. Furthermore, a 2016 meta-analysis found that caffeinated coffee may have greater chemopreventive effects against melanoma than decaffeinated coffee.⁴⁸

Adverse effects

Despite the many potential benefits of coffee, caffeine is a potent drug that should be used with caution.⁴⁹ People with underlying heart problems should avoid caffeine due to concern that it may cause palpitations from tachycardia. It may worsen anxiety problems or depression. Coffee may increase the production of stomach acids, which can worsen acid reflux or stomach ulcers.

Regular coffee intake is associated with a lower risk of mortality, reduced CV events, and a reduction in liver disease progression.

Caffeine is a potent diuretic and may decrease absorption of calcium and cause OA. Caffeine may cause dependence and withdrawal symptoms. Some of the symptoms of withdrawal include drowsiness, headaches, irritability, nausea, and vomiting. It may disrupt sleeping patterns by causing jitters and sleeplessness.⁴⁹ Additionally, large amounts of caffeine may cause overdose and death.

The bottom line

Regular coffee intake is associated with a lower risk of mortality, reduced cardiovascular events, and a reduction in liver disease progression. Coffee may also have some utility for improving cognitive function and reducing the risk of type 2 diabetes. Caffeinated coffee should be limited to no more than 32 oz per day, due to the risk of insomnia, palpitations, anxiety, and gastritis.

Overview

Few natural products have been claimed to successfully treat as many disorders as chocolate. The modern concept of chocolate as food has overshadowed its traditional medicinal use, although recent trials have looked at evidence for some of its traditional uses. Chocolate is processed from the pod of the cacao plant. The earliest evidence for its medical use is in Mayan civilizations, and for most of its approximately 4000-year history, chocolate was consumed as a bitter drink referred to as the “drink of the Gods.” The traditional drink was mixed with water, vanilla, honey, chili peppers, and other spices. Important components in chocolate include flavonoids (antioxidants), cocoa butter, caffeine, theobromine, and phenylethylamine.  

Chocolate has stimulating, anti-inflammatory, neuroprotective, and cardioprotective effects, and improves the bioavailability of nitric oxide, which can improve blood pressure and platelet function.⁵⁰ Epicatechin (an antioxidant) in cocoa is primarily responsible for its favorable impact on vascular endothelium via its effect on both acute and chronic upregulation of nitric oxide production. Other cardiovascular effects are mediated by the anti-inflammatory effects of cocoa polyphenols, and modulated through the activity of NF-kappaB.⁵¹

Multiple studies have shown that chocolate is associated with a reduction in cardiovascular risk.

Dark chocolate appears to have the greatest benefit, as milk binds to antioxidants in chocolate, making them unavailable. Therefore, milk chocolate is not a good antioxidant source. There is no specific amount of chocolate that is known to be ideal, but an average of one to 2 ounces per day is often used in studies.

Cardiovascular effects. Chocolate does contain saturated fat, but a comparative, double-blind study found that short-term use of cocoa powder lowered plasma low-density lipoprotein (LDL) cholesterol, oxidized LDL, and apo B concentrations, and the plasma high-density lipoprotein (HDL) cholesterol concentration increased, relative to baseline in the low-, middle-, and high-cocoa groups.⁵² A small randomized crossover trial without clinical outcomes indicated that chocolate may increase HDL cholesterol without increasing weight.⁵³

A meta-analysis of short-term (2-12 weeks) treatment with dark chocolate/cocoa products showed reductions in LDL and total cholesterol, but no changes in HDL or triglycerides.⁵⁴ Another meta-analysis of RCTs, however, showed no short-term effect of cocoa/chocolate on lipid concentrations.⁵⁵ A randomized, placebo-controlled double-blind study of 62 patients with diabetes and hypertension showed that high polyphenol chocolate improved triglyceride levels.⁵⁶

Chocolate intake was associated with a lower risk of cognitive decline, with the greatest benefit noted in those who averaged more than one chocolate bar per week.

Multiple studies have shown that chocolate is associated with a reduction in cardiovascular risk.^57-59 A best case scenario analysis using a Markov model to predict the long-term effectiveness and cost effectiveness of daily dark chocolate consumption in a population with metabolic syndrome at high risk of cardiovascular disease concluded that daily consumption of dark chocolate can reduce cardiovascular events by 85 per 10,000 population treated over 10 years. The study concluded that $42 could be cost effectively spent per person per year on prevention strategies using dark chocolate.⁵⁹

In addition, a meta-analysis of 7 observational studies showed that high levels of chocolate consumption (any type) were associated with a 29% reduction in stroke compared with the lowest levels of chocolate intake.⁵⁷ Results of a similar meta-analysis from Neurology in 2012 also suggested that moderate chocolate consumption (any type) may lower the risk of stroke.⁶⁰

That said, 2 systematic reviews specifically relating to the risk of coronary heart disease and chocolate intake were inconclusive.^61-62

Blood pressure (BP). An RCT published in JAMA indicates that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved the formation of vasodilative nitric oxide.⁶³ A meta-analysis of 10 RCTs also showed mean BP change in the active cocoa treatment arms across all trials was -4.5 mm Hg (95% confidence interval (CI), -5.9 to -3.2; P<.001) for systolic BP and -2.5 mm Hg (95% CI, -3.9 to -1.2; P<.001) for diastolic BP.⁶⁴

A Cochrane Review meta-analysis of 20 studies revealed a statistically significant BP-reducing effect of flavanol-rich cocoa products compared with control in short-term trials of 2 to 18 weeks' duration.⁶⁵ Because studies have shown improvement in BP with chocolate intake, investigations into a role of chocolate in the prevention of preeclampsia have been undertaken. In some studies, chocolate intake was associated with reduced odds of preeclampsia and gestational hypertension.^66,67

Diabetes. Chocolate may exert significant vascular protection because of its antioxidant properties and possible increase of nitric oxide bioavailability, which can influence glucose uptake. A small trial comparing the effects of either dark or white chocolate bars (which do not contain the polyphenols) showed improved BP and glucose and insulin responses to an oral glucose tolerance test in healthy subjects on dark chocolate, but not white chocolate.⁶⁸ A comparison of chocolate consumption and risk of diabetes in the Physicians’ Health Study showed an inverse relationship between chocolate intake with incident disease, but this association appeared only to apply in younger and normal-body weight men after controlling for comprehensive lifestyles, including total energy consumption.⁶⁹

Fatigue. The effect of chocolate on a person’s energy level has been noted for centuries.⁷⁰ A small randomized trial showed improved energy levels in those treated with higher chocolate intakes. In a double-blind, randomized, clinical pilot crossover study, high cocoa liquor/polyphenol rich chocolate, reduced fatigue in subjects with chronic fatigue syndrome.⁷¹

Anxiety. A small randomized trial showed chocolate decreased anxiety in high-anxiety trait subjects and improved the anxiety level and the energy levels of low-anxiety trait participants.⁷²

Eye effects. The literature presents conflicting evidence regarding the effect of flavonoids on patients with glaucoma and ocular hypertension. However, a meta-analysis showed that flavonoids have a promising role in improving visual function in patients with glaucoma and ocular hypertension, and appear to play a part in both improving and slowing the progression of visual field loss.⁷³

Cognitive decline. Chocolate intake (any type) was associated with a lower risk of cognitive decline (RR = 0.59; 95% CI, 0.38-0.92) with the greatest benefit noted in those who averaged more than one chocolate bar or one tablespoon of cocoa powder per week. This protective effect was observed only among subjects with an average daily consumption of caffeine <75  mg (69% of the participants; RR = 0.50; 95% CI, 0.31-0.82).⁷⁴

The bottom line

Chocolate with high cocoa content (dark chocolate) appears to be safe and beneficial as part of a healthy diet and lifestyle that includes exercise and stress reduction to decrease cardiovascular risk and may improve energy levels.

CORRESPONDENCE
Michael Malone, MD, Family and Community Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033; [email protected].

More than a third of American adults use complementary and alternative medicine.¹ Unfortunately, the public’s enthusiasm for herbal products is not always consistent with the scientific evidence supporting their use. In part one of this series, we discussed the studies that have been done on capsaicin, butterbur, green tea, and peppermint. In this installment, we outline the research on 5 additional remedies: turmeric/curcumin, which may be of benefit in ulcerative colitis; chamomile, which appears to offer relief to patients with anxiety; rosemary, which may help treat alopecia; as well as coffee and cocoa, which may have some cardiovascular benefits (TABLE).

Turmeric/curcumin

Overview

Turmeric (Curcuma longa), a relative of ginger, has been used for 4000 years to treat a variety of conditions.^2,3 Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric.³ Turmeric powder contains 5% curcumin, which is the main biologically active compound. Although it grows in many tropical locations, most turmeric is grown in India, where it is used as a main ingredient in curry. The roots and bulbs of turmeric that are used in medicine are generally boiled and dried, which results in a yellow powder.

Turmeric has been used in both Ayurvedic and Chinese medicine for its anti-inflammatory properties, in the treatment of digestive and liver problems, to fight infections, and to help heal skin diseases and wounds.^3-7

Functional GI disorders. A recent review noted that curcumin has been shown in several preclinical studies and uncontrolled clinical trials to have effects on gut inflammation, gut permeability, and the brain-gut axis, especially in functional GI disorders.⁷ A double-blind, placebo-controlled study from 1989 found that turmeric reduced symptoms of bloating and gas in subjects suffering from undifferentiated dyspepsia.⁸

Ulcerative colitis (UC). A 2012 Cochrane review noted that curcumin appears to be a safe and effective therapy for maintenance of remission in quiescent UC when given as adjunctive therapy along with mesalamine or sulfasalazine.⁹ In a 2015 randomized controlled trial (RCT), the addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects.¹⁰

Osteoarthritis (OA). Because of turmeric’s ability to reduce inflammation, it may help relieve OA pain.³ Clinical evidence is scant for the anti-arthritic efficacy of turmeric dietary supplements, although animal studies indicate that turmeric prevents inflammation through regulation of NF-kappaB-regulated genes that regulate the immune and inflammatory response.⁶ Inflammatory cell influx, joint levels of prostaglandin E2, and periarticular osteoclast formation were also inhibited by turmeric extract treatment.⁶

A 2013 review of turmeric for OA concluded that observational studies and in vitro results are promising for the use of curcumin for OA, but well-designed clinical studies were lacking and are needed to support the efficacy of curcumin in OA patients.¹¹ How­ever, in a 2014 randomized trial of 367 patients, turmeric appeared to be similar in efficacy to ibuprofen for the treatment of pain and disability in adults with knee OA.¹² The curcumin (turmeric) group also had fewer adverse effects.¹²

Cancer. There has been a great deal of research on turmeric’s anti-cancer properties, but clinical evidence is lacking. In vitro evidence, animal studies, and small clinical trials suggest that curcumin may help prevent or treat several types of cancers, but the overall evidence is poor. Nonetheless, curcumin and turmeric have been or are currently being evaluated for the treatment or prevention of prostate, liver, breast, skin, gynecologic, hematologic, pulmonary, thymic, bone, brain, and colon cancer.^13-18

Oral submucous fibrosis. A small randomized trial found improvement in oral function with curcumin lozenges, when compared to placebo, indicating that turmeric may hold promise as a treatment of oral submucous fibrosis.¹⁹

Uveitis. A small pilot study of 32 patients suggested that oral curcumin may be as effective as corticosteroids for uveitis.²⁰

Heart disease. Curcumin may have a cardiovascular protective role, as it has been shown to reduce atherosclerosis, but a reduction in myocardial infarction or stroke has not been documented.²¹

Alzheimer’s dementia. Animal studies have shown a reduction in amyloid plaque formation with curcumin.²²

Adverse effects (and precautions)

Turmeric in food is considered safe. A variety of animal and human studies have also indicated that curcumin is safe and well tolerated, even at very high doses.¹³ However, taking large amounts of turmeric for long periods of time could cause stomach upset and gastric ulcers. In addition, patients with gallstones or bile obstruction should use it with caution due to increased bile production.⁷

Because turmeric may lower blood sugar levels, patients with diabetes should monitor for hypoglycemia when using turmeric in combination with diabetic medications. Similarly, those with bleeding disorders taking blood thinners should use turmeric and curcumin with caution, because it can inhibit platelet aggregation.²³

Although it is safe to eat foods with turmeric during pregnancy, pregnant and breastfeeding women should not take turmeric supplements, as the safety of large doses in pregnancy is unknown.

The bottom line

Turmeric/curcumin has anti-inflammatory properties and may be useful as an adjunct for ulcerative colitis and to improve the symptoms of OA. It may also have anti-carcinogenic properties, although definitive data are lacking. Those with a history of gastrointestinal conditions such as gastric ulcer, patients taking blood thinners, and patients with diabetes who are prone to low blood sugar levels should use turmeric/curcumin with caution.

Overview

Chamomile, a member of the Asteraceae/Compositae family, is one of the oldest herbal medicines. It has been used for hay fever, inflammation, muscle spasms, menstrual disorders, insomnia, ulcers, wounds, gastrointestinal disorders, rheumatic pain, and hemorrhoids. Essential oils of chamomile are used extensively in cosmetics and aromatherapy. Many different preparations have been developed, the most popular being herbal tea.²⁴

A controlled clinical trial of chamomile extract suggested that it may have modest anxiolytic activity in patients with mild to moderate generalized anxiety disorder.

Individuals with a hypersensitivity to plants of the Asteraceae (Compositae) family such as ragweed (Ambrosia spp.), marigold flower (Calendula officinalis), and chrysanthemum (Chrysanthemum spp.) may show a similar reaction to chamomile.²⁵

Anxiety. A controlled clinical trial of chamomile extract for generalized anxiety disorder (GAD) suggested that it may have modest anxiolytic activity in patients with mild to moderate GAD.²⁶ Another randomized, double-blind, placebo-controlled trial found oral chamomile extract was efficacious and well-tolerated in patients experiencing mild to moderate GAD and may provide an alternative therapeutic anxiolytic for patients with mild GAD.²⁵ In addition to its anxiolytic activity, chamomile may also provide clinically meaningful antidepressant activity.²⁶

Insomnia. Chamomile may have some impact on sleep diary measures (total sleep time, sleep efficiency, sleep latency, wake after sleep onset, sleep quality, and number of awakenings) relative to placebo in adults with chronic primary insomnia, according to a small randomized, double-blind, placebo-controlled pilot trial involving 34 patients.²⁷ However, a systematic review found no statistically significant difference between any herbal medicine (including chamomile) and placebo, for clinical efficacy in patients with insomnia. A similar, or smaller, number of adverse events per person were reported with chamomile compared with placebo, suggesting safe use.²⁸

Infantile colic. A small prospective double-blind study on the use of chamomile-containing tea on infantile colic showed statistically significant symptom improvement in tea-treated infants. The study did note, however, that prolonged ingestion of herbal teas may lead to decreased milk intake.^29,30

Adverse effects

As noted earlier, a systematic review found that the number of adverse events per person reported with chamomile was comparable to the number associated with placebo, suggesting that it is safe.²⁸

The bottom line

Chamomile appears to be safe with minimal adverse effects and may be effective for the treatment of anxiety, insomnia, and infantile colic.

Rosemary

Overview

Rosemary, officially known as Rosmarinus officinalis, is a medicinal evergreen plant native to the Mediterranean area that appears to increase microcapillary perfusion.³¹

Topical rosemary oil may be useful in the treatment of alopecia, with minimal adverse effects.

Alopecia. A randomized double-blind controlled trial found that essential oils including rosemary oil (as well as thyme, lavender, and cedarwood) massaged into the scalp improved hair growth in almost half of patients with alopecia areata after 7 months.³² Another randomized trial comparing rosemary oil to minoxidil 2% for androgenetic alopecia showed a significant increase in hair count at the 6-month endpoint compared with the baseline, but no significant difference was found between the study groups regarding hair count either at Month 3 or Month 6 (P >.05). ³¹

Adverse effects

In the randomized trial described above comparing rosemary oil to minoxidil 2%, adverse effects appeared to be rare for topical rosemary oil. Scalp itching was more frequent in the minoxidil group.³¹

The bottom line

Topical rosemary oil may be useful in the treatment of alopecia with minimal adverse effects.

Overview

Coffee is one of the most widely used botanicals with approximately 3.5 billion cups of coffee consumed per day worldwide. It is a popular beverage because of its unique aromatic taste and its use as a central nervous system stimulant. The coffee tree (genus coffea) is found throughout Latin America, Africa, and eastern Asia. Two of the most common commercially grown species are Coffea arabica (Arabicas) and Coffea canephora (Robusta). Processing and roasting methods may differ and produce variations in flavor and aroma. The degree of roasting also affects the caffeine content.

Coffee consumption leads to increased alertness and can boost mental performance. Based on the literature and US Food and Drug Administration recommendations, four 8-oz cups of coffee (about 400 mg of caffeine) daily is an acceptable average amount of caffeine. More than 500 mg/d is considered excessive use of coffee.^33,34

Overall mortality. A 2008 study showed that regular coffee was not associated with increased or decreased mortality in both men and women.³⁵ However, more recent studies show an inverse relationship between mortality and coffee consumption.

Specifically, a 2014 meta-analysis found an inverse relationship between coffee and mortality.³⁶ A large prospective cohort study from 2015 that included 79,234 women and 76,704 men found that drinking coffee was inversely associated with overall mortality.³⁷ In this cohort study, an inverse association were observed for deaths from heart disease, respiratory disease, diabetes, and self-harm.³⁷ While mechanisms were not analyzed, coffee may reduce mortality risk by affecting inflammation, lung function, insulin sensitivity, and depression.

Cardiovascular disease. Coffee consumption may modestly reduce the risk of stroke, according to a prospective cohort study of 83,076 women from the Nurses’ Health Study who were followed for 24 years.³⁸ Reduced cardiovascular mortality was also found in a large prospective cohort study, as noted in the mortality discussion above.³⁷ A 2014 meta-analysis concluded that coffee consumption is inversely associated with cardiovascular mortality. Drinking 3 or 4 cups a day appears to be the amount that may decrease one’s risk of death when compared to those who do not drink coffee at all.³⁶

Liver disease. Friedrich et al performed a study involving 379 patients with end stage liver disease, and found that coffee consumption delayed the progression of disease in patients with both alcoholic liver disease and primary sclerosing cholangitis.³⁹ Coffee consumption also increased long-term survival after liver transplantation.³⁹ However, the study found that coffee did not have any effect on patients with chronic viral hepatitis.

In a 2016 meta-analysis, caffeinated coffee consumption reduced hepatic fibrosis of nonalcoholic fatty liver disease, although caffeine consumption did not reduce the prevalence of nonalcoholic fatty liver disease.⁴⁰ Another meta-analysis, including 16 studies, also found caffeine reduced the risk for hepatic fibrosis and cirrhosis.⁴¹

Depression. Based on 2 different systematic reviews and meta-analyses from 2016, coffee consumption appears to have a significant protective effect, decreasing the risk of developing depression.^40,42

Alzheimer’s disease/dementia. Coffee, tea, and caffeine consumption show promise in reducing the risk of cognitive decline and dementia. Individuals who consume one to 2 cups of coffee per day had a decreased incidence of mild cognitive impairment compared to non-drinkers.⁴³ A 2015 Japanese study also found an inverse association between coffee consumption and dementia among women, nonsmokers, and those who do not drink alcohol.⁴⁴ Most recently, a 2016 study, the Women’s Health Initiative Memory Study, looked at incident dementia rates in women >65 years of age with high vs low caffeine intake. Women with higher caffeine intake were less likely to develop dementia or any cognitive impairment compared with those consuming <64 mg/day.⁴⁵

Type 2 diabetes. A 2009 prospective cohort study, which included 40,011 participants followed for more than 10 years, found that drinking at least 3 cups of coffee or tea was associated with a lowered risk of type 2 diabetes.⁴⁶ A 2009 systematic review of 20 cohort studies showed that high intakes of coffee, decaffeinated coffee, and tea are associated with a reduced risk of diabetes.⁴⁷

A meta-analysis of 12 studies involving 832,956 participants found an inverse relationship between cutaneous melanoma and coffee consumption.

Melanoma. A meta-analysis of 12 studies involving 832,956 participants demon­strated an inverse relationship between cutaneous melanoma and coffee consumption.⁴⁷ The risk of melanoma decreased by 3% and 4% for one cup/day of total coffee and caffeinated coffee consumption, respectively. Furthermore, a 2016 meta-analysis found that caffeinated coffee may have greater chemopreventive effects against melanoma than decaffeinated coffee.⁴⁸

Adverse effects

Despite the many potential benefits of coffee, caffeine is a potent drug that should be used with caution.⁴⁹ People with underlying heart problems should avoid caffeine due to concern that it may cause palpitations from tachycardia. It may worsen anxiety problems or depression. Coffee may increase the production of stomach acids, which can worsen acid reflux or stomach ulcers.

Regular coffee intake is associated with a lower risk of mortality, reduced CV events, and a reduction in liver disease progression.

Caffeine is a potent diuretic and may decrease absorption of calcium and cause OA. Caffeine may cause dependence and withdrawal symptoms. Some of the symptoms of withdrawal include drowsiness, headaches, irritability, nausea, and vomiting. It may disrupt sleeping patterns by causing jitters and sleeplessness.⁴⁹ Additionally, large amounts of caffeine may cause overdose and death.

The bottom line

Regular coffee intake is associated with a lower risk of mortality, reduced cardiovascular events, and a reduction in liver disease progression. Coffee may also have some utility for improving cognitive function and reducing the risk of type 2 diabetes. Caffeinated coffee should be limited to no more than 32 oz per day, due to the risk of insomnia, palpitations, anxiety, and gastritis.

Overview

Few natural products have been claimed to successfully treat as many disorders as chocolate. The modern concept of chocolate as food has overshadowed its traditional medicinal use, although recent trials have looked at evidence for some of its traditional uses. Chocolate is processed from the pod of the cacao plant. The earliest evidence for its medical use is in Mayan civilizations, and for most of its approximately 4000-year history, chocolate was consumed as a bitter drink referred to as the “drink of the Gods.” The traditional drink was mixed with water, vanilla, honey, chili peppers, and other spices. Important components in chocolate include flavonoids (antioxidants), cocoa butter, caffeine, theobromine, and phenylethylamine.  

Chocolate has stimulating, anti-inflammatory, neuroprotective, and cardioprotective effects, and improves the bioavailability of nitric oxide, which can improve blood pressure and platelet function.⁵⁰ Epicatechin (an antioxidant) in cocoa is primarily responsible for its favorable impact on vascular endothelium via its effect on both acute and chronic upregulation of nitric oxide production. Other cardiovascular effects are mediated by the anti-inflammatory effects of cocoa polyphenols, and modulated through the activity of NF-kappaB.⁵¹

Multiple studies have shown that chocolate is associated with a reduction in cardiovascular risk.

Dark chocolate appears to have the greatest benefit, as milk binds to antioxidants in chocolate, making them unavailable. Therefore, milk chocolate is not a good antioxidant source. There is no specific amount of chocolate that is known to be ideal, but an average of one to 2 ounces per day is often used in studies.

Cardiovascular effects. Chocolate does contain saturated fat, but a comparative, double-blind study found that short-term use of cocoa powder lowered plasma low-density lipoprotein (LDL) cholesterol, oxidized LDL, and apo B concentrations, and the plasma high-density lipoprotein (HDL) cholesterol concentration increased, relative to baseline in the low-, middle-, and high-cocoa groups.⁵² A small randomized crossover trial without clinical outcomes indicated that chocolate may increase HDL cholesterol without increasing weight.⁵³

A meta-analysis of short-term (2-12 weeks) treatment with dark chocolate/cocoa products showed reductions in LDL and total cholesterol, but no changes in HDL or triglycerides.⁵⁴ Another meta-analysis of RCTs, however, showed no short-term effect of cocoa/chocolate on lipid concentrations.⁵⁵ A randomized, placebo-controlled double-blind study of 62 patients with diabetes and hypertension showed that high polyphenol chocolate improved triglyceride levels.⁵⁶

Chocolate intake was associated with a lower risk of cognitive decline, with the greatest benefit noted in those who averaged more than one chocolate bar per week.

Multiple studies have shown that chocolate is associated with a reduction in cardiovascular risk.^57-59 A best case scenario analysis using a Markov model to predict the long-term effectiveness and cost effectiveness of daily dark chocolate consumption in a population with metabolic syndrome at high risk of cardiovascular disease concluded that daily consumption of dark chocolate can reduce cardiovascular events by 85 per 10,000 population treated over 10 years. The study concluded that $42 could be cost effectively spent per person per year on prevention strategies using dark chocolate.⁵⁹

In addition, a meta-analysis of 7 observational studies showed that high levels of chocolate consumption (any type) were associated with a 29% reduction in stroke compared with the lowest levels of chocolate intake.⁵⁷ Results of a similar meta-analysis from Neurology in 2012 also suggested that moderate chocolate consumption (any type) may lower the risk of stroke.⁶⁰

That said, 2 systematic reviews specifically relating to the risk of coronary heart disease and chocolate intake were inconclusive.^61-62

Blood pressure (BP). An RCT published in JAMA indicates that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved the formation of vasodilative nitric oxide.⁶³ A meta-analysis of 10 RCTs also showed mean BP change in the active cocoa treatment arms across all trials was -4.5 mm Hg (95% confidence interval (CI), -5.9 to -3.2; P<.001) for systolic BP and -2.5 mm Hg (95% CI, -3.9 to -1.2; P<.001) for diastolic BP.⁶⁴

A Cochrane Review meta-analysis of 20 studies revealed a statistically significant BP-reducing effect of flavanol-rich cocoa products compared with control in short-term trials of 2 to 18 weeks' duration.⁶⁵ Because studies have shown improvement in BP with chocolate intake, investigations into a role of chocolate in the prevention of preeclampsia have been undertaken. In some studies, chocolate intake was associated with reduced odds of preeclampsia and gestational hypertension.^66,67

Diabetes. Chocolate may exert significant vascular protection because of its antioxidant properties and possible increase of nitric oxide bioavailability, which can influence glucose uptake. A small trial comparing the effects of either dark or white chocolate bars (which do not contain the polyphenols) showed improved BP and glucose and insulin responses to an oral glucose tolerance test in healthy subjects on dark chocolate, but not white chocolate.⁶⁸ A comparison of chocolate consumption and risk of diabetes in the Physicians’ Health Study showed an inverse relationship between chocolate intake with incident disease, but this association appeared only to apply in younger and normal-body weight men after controlling for comprehensive lifestyles, including total energy consumption.⁶⁹

Fatigue. The effect of chocolate on a person’s energy level has been noted for centuries.⁷⁰ A small randomized trial showed improved energy levels in those treated with higher chocolate intakes. In a double-blind, randomized, clinical pilot crossover study, high cocoa liquor/polyphenol rich chocolate, reduced fatigue in subjects with chronic fatigue syndrome.⁷¹

Anxiety. A small randomized trial showed chocolate decreased anxiety in high-anxiety trait subjects and improved the anxiety level and the energy levels of low-anxiety trait participants.⁷²

Eye effects. The literature presents conflicting evidence regarding the effect of flavonoids on patients with glaucoma and ocular hypertension. However, a meta-analysis showed that flavonoids have a promising role in improving visual function in patients with glaucoma and ocular hypertension, and appear to play a part in both improving and slowing the progression of visual field loss.⁷³

Cognitive decline. Chocolate intake (any type) was associated with a lower risk of cognitive decline (RR = 0.59; 95% CI, 0.38-0.92) with the greatest benefit noted in those who averaged more than one chocolate bar or one tablespoon of cocoa powder per week. This protective effect was observed only among subjects with an average daily consumption of caffeine <75  mg (69% of the participants; RR = 0.50; 95% CI, 0.31-0.82).⁷⁴

The bottom line

Chocolate with high cocoa content (dark chocolate) appears to be safe and beneficial as part of a healthy diet and lifestyle that includes exercise and stress reduction to decrease cardiovascular risk and may improve energy levels.

CORRESPONDENCE
Michael Malone, MD, Family and Community Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033; [email protected].

More than a third of American adults use complementary and alternative medicine.¹ Unfortunately, the public’s enthusiasm for herbal products is not always consistent with the scientific evidence supporting their use. In part one of this series, we discussed the studies that have been done on capsaicin, butterbur, green tea, and peppermint. In this installment, we outline the research on 5 additional remedies: turmeric/curcumin, which may be of benefit in ulcerative colitis; chamomile, which appears to offer relief to patients with anxiety; rosemary, which may help treat alopecia; as well as coffee and cocoa, which may have some cardiovascular benefits (TABLE).

Turmeric/curcumin

Overview

Turmeric (Curcuma longa), a relative of ginger, has been used for 4000 years to treat a variety of conditions.^2,3 Curcumin is the yellow pigment isolated from the rhizomes of Curcuma longa, commonly known as turmeric.³ Turmeric powder contains 5% curcumin, which is the main biologically active compound. Although it grows in many tropical locations, most turmeric is grown in India, where it is used as a main ingredient in curry. The roots and bulbs of turmeric that are used in medicine are generally boiled and dried, which results in a yellow powder.

Turmeric has been used in both Ayurvedic and Chinese medicine for its anti-inflammatory properties, in the treatment of digestive and liver problems, to fight infections, and to help heal skin diseases and wounds.^3-7

Functional GI disorders. A recent review noted that curcumin has been shown in several preclinical studies and uncontrolled clinical trials to have effects on gut inflammation, gut permeability, and the brain-gut axis, especially in functional GI disorders.⁷ A double-blind, placebo-controlled study from 1989 found that turmeric reduced symptoms of bloating and gas in subjects suffering from undifferentiated dyspepsia.⁸

Ulcerative colitis (UC). A 2012 Cochrane review noted that curcumin appears to be a safe and effective therapy for maintenance of remission in quiescent UC when given as adjunctive therapy along with mesalamine or sulfasalazine.⁹ In a 2015 randomized controlled trial (RCT), the addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects.¹⁰

Osteoarthritis (OA). Because of turmeric’s ability to reduce inflammation, it may help relieve OA pain.³ Clinical evidence is scant for the anti-arthritic efficacy of turmeric dietary supplements, although animal studies indicate that turmeric prevents inflammation through regulation of NF-kappaB-regulated genes that regulate the immune and inflammatory response.⁶ Inflammatory cell influx, joint levels of prostaglandin E2, and periarticular osteoclast formation were also inhibited by turmeric extract treatment.⁶

A 2013 review of turmeric for OA concluded that observational studies and in vitro results are promising for the use of curcumin for OA, but well-designed clinical studies were lacking and are needed to support the efficacy of curcumin in OA patients.¹¹ How­ever, in a 2014 randomized trial of 367 patients, turmeric appeared to be similar in efficacy to ibuprofen for the treatment of pain and disability in adults with knee OA.¹² The curcumin (turmeric) group also had fewer adverse effects.¹²

Cancer. There has been a great deal of research on turmeric’s anti-cancer properties, but clinical evidence is lacking. In vitro evidence, animal studies, and small clinical trials suggest that curcumin may help prevent or treat several types of cancers, but the overall evidence is poor. Nonetheless, curcumin and turmeric have been or are currently being evaluated for the treatment or prevention of prostate, liver, breast, skin, gynecologic, hematologic, pulmonary, thymic, bone, brain, and colon cancer.^13-18

Oral submucous fibrosis. A small randomized trial found improvement in oral function with curcumin lozenges, when compared to placebo, indicating that turmeric may hold promise as a treatment of oral submucous fibrosis.¹⁹

Uveitis. A small pilot study of 32 patients suggested that oral curcumin may be as effective as corticosteroids for uveitis.²⁰

Heart disease. Curcumin may have a cardiovascular protective role, as it has been shown to reduce atherosclerosis, but a reduction in myocardial infarction or stroke has not been documented.²¹

Alzheimer’s dementia. Animal studies have shown a reduction in amyloid plaque formation with curcumin.²²

Adverse effects (and precautions)

Turmeric in food is considered safe. A variety of animal and human studies have also indicated that curcumin is safe and well tolerated, even at very high doses.¹³ However, taking large amounts of turmeric for long periods of time could cause stomach upset and gastric ulcers. In addition, patients with gallstones or bile obstruction should use it with caution due to increased bile production.⁷

Because turmeric may lower blood sugar levels, patients with diabetes should monitor for hypoglycemia when using turmeric in combination with diabetic medications. Similarly, those with bleeding disorders taking blood thinners should use turmeric and curcumin with caution, because it can inhibit platelet aggregation.²³

Although it is safe to eat foods with turmeric during pregnancy, pregnant and breastfeeding women should not take turmeric supplements, as the safety of large doses in pregnancy is unknown.

The bottom line

Turmeric/curcumin has anti-inflammatory properties and may be useful as an adjunct for ulcerative colitis and to improve the symptoms of OA. It may also have anti-carcinogenic properties, although definitive data are lacking. Those with a history of gastrointestinal conditions such as gastric ulcer, patients taking blood thinners, and patients with diabetes who are prone to low blood sugar levels should use turmeric/curcumin with caution.

Overview

Chamomile, a member of the Asteraceae/Compositae family, is one of the oldest herbal medicines. It has been used for hay fever, inflammation, muscle spasms, menstrual disorders, insomnia, ulcers, wounds, gastrointestinal disorders, rheumatic pain, and hemorrhoids. Essential oils of chamomile are used extensively in cosmetics and aromatherapy. Many different preparations have been developed, the most popular being herbal tea.²⁴

A controlled clinical trial of chamomile extract suggested that it may have modest anxiolytic activity in patients with mild to moderate generalized anxiety disorder.

Individuals with a hypersensitivity to plants of the Asteraceae (Compositae) family such as ragweed (Ambrosia spp.), marigold flower (Calendula officinalis), and chrysanthemum (Chrysanthemum spp.) may show a similar reaction to chamomile.²⁵

Anxiety. A controlled clinical trial of chamomile extract for generalized anxiety disorder (GAD) suggested that it may have modest anxiolytic activity in patients with mild to moderate GAD.²⁶ Another randomized, double-blind, placebo-controlled trial found oral chamomile extract was efficacious and well-tolerated in patients experiencing mild to moderate GAD and may provide an alternative therapeutic anxiolytic for patients with mild GAD.²⁵ In addition to its anxiolytic activity, chamomile may also provide clinically meaningful antidepressant activity.²⁶

Insomnia. Chamomile may have some impact on sleep diary measures (total sleep time, sleep efficiency, sleep latency, wake after sleep onset, sleep quality, and number of awakenings) relative to placebo in adults with chronic primary insomnia, according to a small randomized, double-blind, placebo-controlled pilot trial involving 34 patients.²⁷ However, a systematic review found no statistically significant difference between any herbal medicine (including chamomile) and placebo, for clinical efficacy in patients with insomnia. A similar, or smaller, number of adverse events per person were reported with chamomile compared with placebo, suggesting safe use.²⁸

Infantile colic. A small prospective double-blind study on the use of chamomile-containing tea on infantile colic showed statistically significant symptom improvement in tea-treated infants. The study did note, however, that prolonged ingestion of herbal teas may lead to decreased milk intake.^29,30

Adverse effects

As noted earlier, a systematic review found that the number of adverse events per person reported with chamomile was comparable to the number associated with placebo, suggesting that it is safe.²⁸

The bottom line

Chamomile appears to be safe with minimal adverse effects and may be effective for the treatment of anxiety, insomnia, and infantile colic.

Rosemary

Overview

Rosemary, officially known as Rosmarinus officinalis, is a medicinal evergreen plant native to the Mediterranean area that appears to increase microcapillary perfusion.³¹

Topical rosemary oil may be useful in the treatment of alopecia, with minimal adverse effects.

Alopecia. A randomized double-blind controlled trial found that essential oils including rosemary oil (as well as thyme, lavender, and cedarwood) massaged into the scalp improved hair growth in almost half of patients with alopecia areata after 7 months.³² Another randomized trial comparing rosemary oil to minoxidil 2% for androgenetic alopecia showed a significant increase in hair count at the 6-month endpoint compared with the baseline, but no significant difference was found between the study groups regarding hair count either at Month 3 or Month 6 (P >.05). ³¹

Adverse effects

In the randomized trial described above comparing rosemary oil to minoxidil 2%, adverse effects appeared to be rare for topical rosemary oil. Scalp itching was more frequent in the minoxidil group.³¹

The bottom line

Topical rosemary oil may be useful in the treatment of alopecia with minimal adverse effects.

Overview

Coffee is one of the most widely used botanicals with approximately 3.5 billion cups of coffee consumed per day worldwide. It is a popular beverage because of its unique aromatic taste and its use as a central nervous system stimulant. The coffee tree (genus coffea) is found throughout Latin America, Africa, and eastern Asia. Two of the most common commercially grown species are Coffea arabica (Arabicas) and Coffea canephora (Robusta). Processing and roasting methods may differ and produce variations in flavor and aroma. The degree of roasting also affects the caffeine content.

Coffee consumption leads to increased alertness and can boost mental performance. Based on the literature and US Food and Drug Administration recommendations, four 8-oz cups of coffee (about 400 mg of caffeine) daily is an acceptable average amount of caffeine. More than 500 mg/d is considered excessive use of coffee.^33,34

Overall mortality. A 2008 study showed that regular coffee was not associated with increased or decreased mortality in both men and women.³⁵ However, more recent studies show an inverse relationship between mortality and coffee consumption.

Specifically, a 2014 meta-analysis found an inverse relationship between coffee and mortality.³⁶ A large prospective cohort study from 2015 that included 79,234 women and 76,704 men found that drinking coffee was inversely associated with overall mortality.³⁷ In this cohort study, an inverse association were observed for deaths from heart disease, respiratory disease, diabetes, and self-harm.³⁷ While mechanisms were not analyzed, coffee may reduce mortality risk by affecting inflammation, lung function, insulin sensitivity, and depression.

Cardiovascular disease. Coffee consumption may modestly reduce the risk of stroke, according to a prospective cohort study of 83,076 women from the Nurses’ Health Study who were followed for 24 years.³⁸ Reduced cardiovascular mortality was also found in a large prospective cohort study, as noted in the mortality discussion above.³⁷ A 2014 meta-analysis concluded that coffee consumption is inversely associated with cardiovascular mortality. Drinking 3 or 4 cups a day appears to be the amount that may decrease one’s risk of death when compared to those who do not drink coffee at all.³⁶

Liver disease. Friedrich et al performed a study involving 379 patients with end stage liver disease, and found that coffee consumption delayed the progression of disease in patients with both alcoholic liver disease and primary sclerosing cholangitis.³⁹ Coffee consumption also increased long-term survival after liver transplantation.³⁹ However, the study found that coffee did not have any effect on patients with chronic viral hepatitis.

In a 2016 meta-analysis, caffeinated coffee consumption reduced hepatic fibrosis of nonalcoholic fatty liver disease, although caffeine consumption did not reduce the prevalence of nonalcoholic fatty liver disease.⁴⁰ Another meta-analysis, including 16 studies, also found caffeine reduced the risk for hepatic fibrosis and cirrhosis.⁴¹

Depression. Based on 2 different systematic reviews and meta-analyses from 2016, coffee consumption appears to have a significant protective effect, decreasing the risk of developing depression.^40,42

Alzheimer’s disease/dementia. Coffee, tea, and caffeine consumption show promise in reducing the risk of cognitive decline and dementia. Individuals who consume one to 2 cups of coffee per day had a decreased incidence of mild cognitive impairment compared to non-drinkers.⁴³ A 2015 Japanese study also found an inverse association between coffee consumption and dementia among women, nonsmokers, and those who do not drink alcohol.⁴⁴ Most recently, a 2016 study, the Women’s Health Initiative Memory Study, looked at incident dementia rates in women >65 years of age with high vs low caffeine intake. Women with higher caffeine intake were less likely to develop dementia or any cognitive impairment compared with those consuming <64 mg/day.⁴⁵

Type 2 diabetes. A 2009 prospective cohort study, which included 40,011 participants followed for more than 10 years, found that drinking at least 3 cups of coffee or tea was associated with a lowered risk of type 2 diabetes.⁴⁶ A 2009 systematic review of 20 cohort studies showed that high intakes of coffee, decaffeinated coffee, and tea are associated with a reduced risk of diabetes.⁴⁷

A meta-analysis of 12 studies involving 832,956 participants found an inverse relationship between cutaneous melanoma and coffee consumption.

Melanoma. A meta-analysis of 12 studies involving 832,956 participants demon­strated an inverse relationship between cutaneous melanoma and coffee consumption.⁴⁷ The risk of melanoma decreased by 3% and 4% for one cup/day of total coffee and caffeinated coffee consumption, respectively. Furthermore, a 2016 meta-analysis found that caffeinated coffee may have greater chemopreventive effects against melanoma than decaffeinated coffee.⁴⁸

Adverse effects

Despite the many potential benefits of coffee, caffeine is a potent drug that should be used with caution.⁴⁹ People with underlying heart problems should avoid caffeine due to concern that it may cause palpitations from tachycardia. It may worsen anxiety problems or depression. Coffee may increase the production of stomach acids, which can worsen acid reflux or stomach ulcers.

Regular coffee intake is associated with a lower risk of mortality, reduced CV events, and a reduction in liver disease progression.

Caffeine is a potent diuretic and may decrease absorption of calcium and cause OA. Caffeine may cause dependence and withdrawal symptoms. Some of the symptoms of withdrawal include drowsiness, headaches, irritability, nausea, and vomiting. It may disrupt sleeping patterns by causing jitters and sleeplessness.⁴⁹ Additionally, large amounts of caffeine may cause overdose and death.

The bottom line

Regular coffee intake is associated with a lower risk of mortality, reduced cardiovascular events, and a reduction in liver disease progression. Coffee may also have some utility for improving cognitive function and reducing the risk of type 2 diabetes. Caffeinated coffee should be limited to no more than 32 oz per day, due to the risk of insomnia, palpitations, anxiety, and gastritis.

Overview

Few natural products have been claimed to successfully treat as many disorders as chocolate. The modern concept of chocolate as food has overshadowed its traditional medicinal use, although recent trials have looked at evidence for some of its traditional uses. Chocolate is processed from the pod of the cacao plant. The earliest evidence for its medical use is in Mayan civilizations, and for most of its approximately 4000-year history, chocolate was consumed as a bitter drink referred to as the “drink of the Gods.” The traditional drink was mixed with water, vanilla, honey, chili peppers, and other spices. Important components in chocolate include flavonoids (antioxidants), cocoa butter, caffeine, theobromine, and phenylethylamine.  

Chocolate has stimulating, anti-inflammatory, neuroprotective, and cardioprotective effects, and improves the bioavailability of nitric oxide, which can improve blood pressure and platelet function.⁵⁰ Epicatechin (an antioxidant) in cocoa is primarily responsible for its favorable impact on vascular endothelium via its effect on both acute and chronic upregulation of nitric oxide production. Other cardiovascular effects are mediated by the anti-inflammatory effects of cocoa polyphenols, and modulated through the activity of NF-kappaB.⁵¹

Multiple studies have shown that chocolate is associated with a reduction in cardiovascular risk.

Dark chocolate appears to have the greatest benefit, as milk binds to antioxidants in chocolate, making them unavailable. Therefore, milk chocolate is not a good antioxidant source. There is no specific amount of chocolate that is known to be ideal, but an average of one to 2 ounces per day is often used in studies.

Cardiovascular effects. Chocolate does contain saturated fat, but a comparative, double-blind study found that short-term use of cocoa powder lowered plasma low-density lipoprotein (LDL) cholesterol, oxidized LDL, and apo B concentrations, and the plasma high-density lipoprotein (HDL) cholesterol concentration increased, relative to baseline in the low-, middle-, and high-cocoa groups.⁵² A small randomized crossover trial without clinical outcomes indicated that chocolate may increase HDL cholesterol without increasing weight.⁵³

A meta-analysis of short-term (2-12 weeks) treatment with dark chocolate/cocoa products showed reductions in LDL and total cholesterol, but no changes in HDL or triglycerides.⁵⁴ Another meta-analysis of RCTs, however, showed no short-term effect of cocoa/chocolate on lipid concentrations.⁵⁵ A randomized, placebo-controlled double-blind study of 62 patients with diabetes and hypertension showed that high polyphenol chocolate improved triglyceride levels.⁵⁶

Chocolate intake was associated with a lower risk of cognitive decline, with the greatest benefit noted in those who averaged more than one chocolate bar per week.

Multiple studies have shown that chocolate is associated with a reduction in cardiovascular risk.^57-59 A best case scenario analysis using a Markov model to predict the long-term effectiveness and cost effectiveness of daily dark chocolate consumption in a population with metabolic syndrome at high risk of cardiovascular disease concluded that daily consumption of dark chocolate can reduce cardiovascular events by 85 per 10,000 population treated over 10 years. The study concluded that $42 could be cost effectively spent per person per year on prevention strategies using dark chocolate.⁵⁹

In addition, a meta-analysis of 7 observational studies showed that high levels of chocolate consumption (any type) were associated with a 29% reduction in stroke compared with the lowest levels of chocolate intake.⁵⁷ Results of a similar meta-analysis from Neurology in 2012 also suggested that moderate chocolate consumption (any type) may lower the risk of stroke.⁶⁰

That said, 2 systematic reviews specifically relating to the risk of coronary heart disease and chocolate intake were inconclusive.^61-62

Blood pressure (BP). An RCT published in JAMA indicates that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved the formation of vasodilative nitric oxide.⁶³ A meta-analysis of 10 RCTs also showed mean BP change in the active cocoa treatment arms across all trials was -4.5 mm Hg (95% confidence interval (CI), -5.9 to -3.2; P<.001) for systolic BP and -2.5 mm Hg (95% CI, -3.9 to -1.2; P<.001) for diastolic BP.⁶⁴

A Cochrane Review meta-analysis of 20 studies revealed a statistically significant BP-reducing effect of flavanol-rich cocoa products compared with control in short-term trials of 2 to 18 weeks' duration.⁶⁵ Because studies have shown improvement in BP with chocolate intake, investigations into a role of chocolate in the prevention of preeclampsia have been undertaken. In some studies, chocolate intake was associated with reduced odds of preeclampsia and gestational hypertension.^66,67

Diabetes. Chocolate may exert significant vascular protection because of its antioxidant properties and possible increase of nitric oxide bioavailability, which can influence glucose uptake. A small trial comparing the effects of either dark or white chocolate bars (which do not contain the polyphenols) showed improved BP and glucose and insulin responses to an oral glucose tolerance test in healthy subjects on dark chocolate, but not white chocolate.⁶⁸ A comparison of chocolate consumption and risk of diabetes in the Physicians’ Health Study showed an inverse relationship between chocolate intake with incident disease, but this association appeared only to apply in younger and normal-body weight men after controlling for comprehensive lifestyles, including total energy consumption.⁶⁹

Fatigue. The effect of chocolate on a person’s energy level has been noted for centuries.⁷⁰ A small randomized trial showed improved energy levels in those treated with higher chocolate intakes. In a double-blind, randomized, clinical pilot crossover study, high cocoa liquor/polyphenol rich chocolate, reduced fatigue in subjects with chronic fatigue syndrome.⁷¹

Anxiety. A small randomized trial showed chocolate decreased anxiety in high-anxiety trait subjects and improved the anxiety level and the energy levels of low-anxiety trait participants.⁷²

Eye effects. The literature presents conflicting evidence regarding the effect of flavonoids on patients with glaucoma and ocular hypertension. However, a meta-analysis showed that flavonoids have a promising role in improving visual function in patients with glaucoma and ocular hypertension, and appear to play a part in both improving and slowing the progression of visual field loss.⁷³

Cognitive decline. Chocolate intake (any type) was associated with a lower risk of cognitive decline (RR = 0.59; 95% CI, 0.38-0.92) with the greatest benefit noted in those who averaged more than one chocolate bar or one tablespoon of cocoa powder per week. This protective effect was observed only among subjects with an average daily consumption of caffeine <75  mg (69% of the participants; RR = 0.50; 95% CI, 0.31-0.82).⁷⁴

The bottom line

Chocolate with high cocoa content (dark chocolate) appears to be safe and beneficial as part of a healthy diet and lifestyle that includes exercise and stress reduction to decrease cardiovascular risk and may improve energy levels.

CORRESPONDENCE
Michael Malone, MD, Family and Community Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033; [email protected].

The Food and Drug Administration has granted priority review to Novartis for their severe aplastic anemia drug.

Eltrombopag (Promacta) is being evaluated for the first-line treatment of severe aplastic anemia (SAA) in combination with standard immunosuppressive therapy (IST). The drug is already approved in the United States for treatment of refractory SAA patients. It is also approved for treatment of chronic immune thrombocytopenia in adults and children who are refractory to other treatments or patients with chronic hepatitis C virus. [[{"fid":"","view_mode":"","fields":{"format":"","field_file_image_alt_text[und][0][value]":"","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"","field_file_image_caption[und][0][format]":"filtered_html"},"type":"media","attributes":{"class":"media-element file-"},"field_deltas":{"1":{"field_file_image_caption[und][0][format]":"filtered_html"}}}]]

The priority review status was granted based on preliminary findings showing that eltrombopag plus IST outperformed IST alone in treatment-naïve patients. The study showed that 52% of newly diagnosed patients achieved a complete response at 6 months with eltrombopag plus IST, which was 35% higher than patients treated with IST alone. The overall response rate was 85% at 6 months in the eltrombopag group, according to Novartis.

The drugmaker received a breakthrough therapy designation from the FDA for eltrombopag for first-line use in SAA in January 2018.

[email protected]

The Food and Drug Administration has granted priority review to Novartis for their severe aplastic anemia drug.

Eltrombopag (Promacta) is being evaluated for the first-line treatment of severe aplastic anemia (SAA) in combination with standard immunosuppressive therapy (IST). The drug is already approved in the United States for treatment of refractory SAA patients. It is also approved for treatment of chronic immune thrombocytopenia in adults and children who are refractory to other treatments or patients with chronic hepatitis C virus. [[{"fid":"","view_mode":"","fields":{"format":"","field_file_image_alt_text[und][0][value]":"","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"","field_file_image_caption[und][0][format]":"filtered_html"},"type":"media","attributes":{"class":"media-element file-"},"field_deltas":{"1":{"field_file_image_caption[und][0][format]":"filtered_html"}}}]]

The priority review status was granted based on preliminary findings showing that eltrombopag plus IST outperformed IST alone in treatment-naïve patients. The study showed that 52% of newly diagnosed patients achieved a complete response at 6 months with eltrombopag plus IST, which was 35% higher than patients treated with IST alone. The overall response rate was 85% at 6 months in the eltrombopag group, according to Novartis.

The drugmaker received a breakthrough therapy designation from the FDA for eltrombopag for first-line use in SAA in January 2018.

[email protected]

The Food and Drug Administration has granted priority review to Novartis for their severe aplastic anemia drug.

Eltrombopag (Promacta) is being evaluated for the first-line treatment of severe aplastic anemia (SAA) in combination with standard immunosuppressive therapy (IST). The drug is already approved in the United States for treatment of refractory SAA patients. It is also approved for treatment of chronic immune thrombocytopenia in adults and children who are refractory to other treatments or patients with chronic hepatitis C virus. [[{"fid":"","view_mode":"","fields":{"format":"","field_file_image_alt_text[und][0][value]":"","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][value]":"","field_file_image_caption[und][0][format]":"filtered_html"},"type":"media","attributes":{"class":"media-element file-"},"field_deltas":{"1":{"field_file_image_caption[und][0][format]":"filtered_html"}}}]]

The priority review status was granted based on preliminary findings showing that eltrombopag plus IST outperformed IST alone in treatment-naïve patients. The study showed that 52% of newly diagnosed patients achieved a complete response at 6 months with eltrombopag plus IST, which was 35% higher than patients treated with IST alone. The overall response rate was 85% at 6 months in the eltrombopag group, according to Novartis.

The drugmaker received a breakthrough therapy designation from the FDA for eltrombopag for first-line use in SAA in January 2018.

[email protected]

CHICAGO – Adding ibrutinib to rituximab improved progression-free survival in patients with Waldenström’s macroglobulinemia, results of a randomized phase 3 trial show.

The results make ibrutinib plus rituximab “a new standard of care” for the disease, said investigator Meletios A. Dimopoulos, MD, with the Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Greece.

“This is a combination with remarkable activity as far as progression-free survival is concerned, and well tolerated,” Dr. Dimopoulos said in a presentation of the data here at the 2018 annual meeting of the American Society of Clinical Oncology (ASCO).

Ibrutinib, a BTK inhibitor, was approved as a single agent in 2015 for the treatment of Waldenström’s macroglobulinemia.* Clinical practice guidelines from the National Comprehensive Cancer Network (NCCN) list ibrutinib as an “other” recommended regimen, noting that study data show a “lower overall and absence of major responses” reported for MYD88 wild-type patients.Rituximab alone and in combination with other agents has clinical activity in Waldenström’s. Moreover, preclinical studies have shown that rituximab and ibrutinib have synergistic activity, Dr. Dimopoulos said, presenting data from the iNNOVATE Study Group and the European Consortium for Waldenström’s Macroglobulinemia that was published concurrently in the New England Journal of Medicine.

They initiated a study of 150 symptomatic patients randomized to either ibrutinib plus rituximab or placebo plus rituximab, with a primary end point of progression-free survival.

They also assessed mutational status of MYD88 and CXCR4 in bone marrow samples, given that previous data suggest outcomes of ibrutinib treatment for this disease depend on MYD88 and CXCR4 mutational status, they said in the report.

Progression-free survival at 30 months was 82% for ibrutinib plus rituximab, compared to 28% for placebo plus rituximab (hazard ratio for progression or death, 0.20; P less than 0.001). Further, ibrutinib and rituximab had a benefit that was independent of the MYD88 or CXCR4 genotype, the investigators reported.

“Response rates with ibrutinib–rituximab were similar across different CXCR4 genotypes, but were slightly lower among patients who did not have the activating MYD88 L265P mutation, which triggers the growth of malignant cells through BTK and hematopoietic-cell kinase, both of which are targeted by ibrutinib,” they wrote.

Atrial fibrillation of grade 3 or higher occurred in 12% of the ibrutinib-rituximab and in 1% of placebo-rituximab groups. In the ibrutinib-rituximab group, the majority of these cases occurred in patients older than 75 years of age, Dr. Dimopoulos reported at ASCO.

Grade 3 or greater hypertension occurred in 13% and 4% of the ibrutinib-rituximab and placebo-rituximab groups respectively, while respiratory tract infections occurred in 4% and 0%. Conversely, the ibrutinib-rituximab arm had a lower rate of grade 3 or greater infusion reactions (1% vs. 16%), he said.

Based on this report, ibrutinib plus rituximab is “appealing, primarily in MYD88-mutated patients, which is the vast majority of Waldenström’s patients,” said Craig Hofmeister, MD, MPH, who commented on the study in a ASCO presentation discussing the results of this trial.

Dr. Hofmeister, of Winship Cancer Institute, Emory University, Atlanta, noted the numerically lower response rate in patients without the MYD88 mutation “makes me wonder whether I would want to have ibrutinib if I was MYD88 wild type.”

Atrial fibrillation and infections on the ibrutinib-rituximab regimen may require close monitoring and should be managed appropriately, he added. “Atrial fibrillation seems to be a consistent theme with ibrutinib, certainly in patients who are older and have probably more heart disease.”

The study (NCT02165397) was funded by Pharmacyclics and Janssen Research and Development. Dr. Dimopoulos reported personal fees from Amgen, Celgene, Janssen, and Takeda, outside of the submitted work. Co-authors reported disclosures related to Pharmacyclics, Bristol-Myers Squibb, Gilead, Roche, and AbbVie, among others. Dr. Hofmeister had no relevant financial disclosures.

SOURCE: Dimopoulos MA, et al. N Engl J Med. 2018 Jun 1. ASCO Abstract 8003.

*Correction, 8/27/2018: An earlier version of this story misstated the date of ibrutinib's approval as a single agent in the treatment of Waldenström’s macroglobulinemia.

CHICAGO – Adding ibrutinib to rituximab improved progression-free survival in patients with Waldenström’s macroglobulinemia, results of a randomized phase 3 trial show.

The results make ibrutinib plus rituximab “a new standard of care” for the disease, said investigator Meletios A. Dimopoulos, MD, with the Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Greece.

“This is a combination with remarkable activity as far as progression-free survival is concerned, and well tolerated,” Dr. Dimopoulos said in a presentation of the data here at the 2018 annual meeting of the American Society of Clinical Oncology (ASCO).

Ibrutinib, a BTK inhibitor, was approved as a single agent in 2015 for the treatment of Waldenström’s macroglobulinemia.* Clinical practice guidelines from the National Comprehensive Cancer Network (NCCN) list ibrutinib as an “other” recommended regimen, noting that study data show a “lower overall and absence of major responses” reported for MYD88 wild-type patients.Rituximab alone and in combination with other agents has clinical activity in Waldenström’s. Moreover, preclinical studies have shown that rituximab and ibrutinib have synergistic activity, Dr. Dimopoulos said, presenting data from the iNNOVATE Study Group and the European Consortium for Waldenström’s Macroglobulinemia that was published concurrently in the New England Journal of Medicine.

They initiated a study of 150 symptomatic patients randomized to either ibrutinib plus rituximab or placebo plus rituximab, with a primary end point of progression-free survival.

They also assessed mutational status of MYD88 and CXCR4 in bone marrow samples, given that previous data suggest outcomes of ibrutinib treatment for this disease depend on MYD88 and CXCR4 mutational status, they said in the report.

Progression-free survival at 30 months was 82% for ibrutinib plus rituximab, compared to 28% for placebo plus rituximab (hazard ratio for progression or death, 0.20; P less than 0.001). Further, ibrutinib and rituximab had a benefit that was independent of the MYD88 or CXCR4 genotype, the investigators reported.

“Response rates with ibrutinib–rituximab were similar across different CXCR4 genotypes, but were slightly lower among patients who did not have the activating MYD88 L265P mutation, which triggers the growth of malignant cells through BTK and hematopoietic-cell kinase, both of which are targeted by ibrutinib,” they wrote.

Atrial fibrillation of grade 3 or higher occurred in 12% of the ibrutinib-rituximab and in 1% of placebo-rituximab groups. In the ibrutinib-rituximab group, the majority of these cases occurred in patients older than 75 years of age, Dr. Dimopoulos reported at ASCO.

Grade 3 or greater hypertension occurred in 13% and 4% of the ibrutinib-rituximab and placebo-rituximab groups respectively, while respiratory tract infections occurred in 4% and 0%. Conversely, the ibrutinib-rituximab arm had a lower rate of grade 3 or greater infusion reactions (1% vs. 16%), he said.

Based on this report, ibrutinib plus rituximab is “appealing, primarily in MYD88-mutated patients, which is the vast majority of Waldenström’s patients,” said Craig Hofmeister, MD, MPH, who commented on the study in a ASCO presentation discussing the results of this trial.

Dr. Hofmeister, of Winship Cancer Institute, Emory University, Atlanta, noted the numerically lower response rate in patients without the MYD88 mutation “makes me wonder whether I would want to have ibrutinib if I was MYD88 wild type.”

Atrial fibrillation and infections on the ibrutinib-rituximab regimen may require close monitoring and should be managed appropriately, he added. “Atrial fibrillation seems to be a consistent theme with ibrutinib, certainly in patients who are older and have probably more heart disease.”

The study (NCT02165397) was funded by Pharmacyclics and Janssen Research and Development. Dr. Dimopoulos reported personal fees from Amgen, Celgene, Janssen, and Takeda, outside of the submitted work. Co-authors reported disclosures related to Pharmacyclics, Bristol-Myers Squibb, Gilead, Roche, and AbbVie, among others. Dr. Hofmeister had no relevant financial disclosures.

SOURCE: Dimopoulos MA, et al. N Engl J Med. 2018 Jun 1. ASCO Abstract 8003.

*Correction, 8/27/2018: An earlier version of this story misstated the date of ibrutinib's approval as a single agent in the treatment of Waldenström’s macroglobulinemia.

CHICAGO – Adding ibrutinib to rituximab improved progression-free survival in patients with Waldenström’s macroglobulinemia, results of a randomized phase 3 trial show.

The results make ibrutinib plus rituximab “a new standard of care” for the disease, said investigator Meletios A. Dimopoulos, MD, with the Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Greece.

“This is a combination with remarkable activity as far as progression-free survival is concerned, and well tolerated,” Dr. Dimopoulos said in a presentation of the data here at the 2018 annual meeting of the American Society of Clinical Oncology (ASCO).

Ibrutinib, a BTK inhibitor, was approved as a single agent in 2015 for the treatment of Waldenström’s macroglobulinemia.* Clinical practice guidelines from the National Comprehensive Cancer Network (NCCN) list ibrutinib as an “other” recommended regimen, noting that study data show a “lower overall and absence of major responses” reported for MYD88 wild-type patients.Rituximab alone and in combination with other agents has clinical activity in Waldenström’s. Moreover, preclinical studies have shown that rituximab and ibrutinib have synergistic activity, Dr. Dimopoulos said, presenting data from the iNNOVATE Study Group and the European Consortium for Waldenström’s Macroglobulinemia that was published concurrently in the New England Journal of Medicine.

They initiated a study of 150 symptomatic patients randomized to either ibrutinib plus rituximab or placebo plus rituximab, with a primary end point of progression-free survival.

They also assessed mutational status of MYD88 and CXCR4 in bone marrow samples, given that previous data suggest outcomes of ibrutinib treatment for this disease depend on MYD88 and CXCR4 mutational status, they said in the report.

Progression-free survival at 30 months was 82% for ibrutinib plus rituximab, compared to 28% for placebo plus rituximab (hazard ratio for progression or death, 0.20; P less than 0.001). Further, ibrutinib and rituximab had a benefit that was independent of the MYD88 or CXCR4 genotype, the investigators reported.

“Response rates with ibrutinib–rituximab were similar across different CXCR4 genotypes, but were slightly lower among patients who did not have the activating MYD88 L265P mutation, which triggers the growth of malignant cells through BTK and hematopoietic-cell kinase, both of which are targeted by ibrutinib,” they wrote.

Atrial fibrillation of grade 3 or higher occurred in 12% of the ibrutinib-rituximab and in 1% of placebo-rituximab groups. In the ibrutinib-rituximab group, the majority of these cases occurred in patients older than 75 years of age, Dr. Dimopoulos reported at ASCO.

Grade 3 or greater hypertension occurred in 13% and 4% of the ibrutinib-rituximab and placebo-rituximab groups respectively, while respiratory tract infections occurred in 4% and 0%. Conversely, the ibrutinib-rituximab arm had a lower rate of grade 3 or greater infusion reactions (1% vs. 16%), he said.

Based on this report, ibrutinib plus rituximab is “appealing, primarily in MYD88-mutated patients, which is the vast majority of Waldenström’s patients,” said Craig Hofmeister, MD, MPH, who commented on the study in a ASCO presentation discussing the results of this trial.

Dr. Hofmeister, of Winship Cancer Institute, Emory University, Atlanta, noted the numerically lower response rate in patients without the MYD88 mutation “makes me wonder whether I would want to have ibrutinib if I was MYD88 wild type.”

Atrial fibrillation and infections on the ibrutinib-rituximab regimen may require close monitoring and should be managed appropriately, he added. “Atrial fibrillation seems to be a consistent theme with ibrutinib, certainly in patients who are older and have probably more heart disease.”

The study (NCT02165397) was funded by Pharmacyclics and Janssen Research and Development. Dr. Dimopoulos reported personal fees from Amgen, Celgene, Janssen, and Takeda, outside of the submitted work. Co-authors reported disclosures related to Pharmacyclics, Bristol-Myers Squibb, Gilead, Roche, and AbbVie, among others. Dr. Hofmeister had no relevant financial disclosures.

SOURCE: Dimopoulos MA, et al. N Engl J Med. 2018 Jun 1. ASCO Abstract 8003.

*Correction, 8/27/2018: An earlier version of this story misstated the date of ibrutinib's approval as a single agent in the treatment of Waldenström’s macroglobulinemia.

In his bimonthly podcast, Dr Henry, the JCSO Editor-in-Chief, discusses a round-up by JCSO Editor Dr Howard Burris of the top takeaways from this year’s annual ASCO meeting, as well as a series of articles focusing on CAR T-cell therapies. He also looks at reports on psychosocial factors and treatment satisfaction after radical prostatectomy; the impact of inpatient rehabilitation on outcomes for patients with cancer; and the long-term effects of posttreatment exercise on pain in young women with breast cancer. Patient-specific cases of carcinoma of the colon in a child, managing severe radiation dermatitis after head and neck radiotherapy, striking rash in a patient on a checkpoint inhibitor, and a small gastric GIST with high mitotic index are also included. Dr Henry rounds off his comments with an examination of the challenges presented by tumor heterogeneity in the war on cancer.

Listen to the podcast below

In his bimonthly podcast, Dr Henry, the JCSO Editor-in-Chief, discusses a round-up by JCSO Editor Dr Howard Burris of the top takeaways from this year’s annual ASCO meeting, as well as a series of articles focusing on CAR T-cell therapies. He also looks at reports on psychosocial factors and treatment satisfaction after radical prostatectomy; the impact of inpatient rehabilitation on outcomes for patients with cancer; and the long-term effects of posttreatment exercise on pain in young women with breast cancer. Patient-specific cases of carcinoma of the colon in a child, managing severe radiation dermatitis after head and neck radiotherapy, striking rash in a patient on a checkpoint inhibitor, and a small gastric GIST with high mitotic index are also included. Dr Henry rounds off his comments with an examination of the challenges presented by tumor heterogeneity in the war on cancer.

Listen to the podcast below

In his bimonthly podcast, Dr Henry, the JCSO Editor-in-Chief, discusses a round-up by JCSO Editor Dr Howard Burris of the top takeaways from this year’s annual ASCO meeting, as well as a series of articles focusing on CAR T-cell therapies. He also looks at reports on psychosocial factors and treatment satisfaction after radical prostatectomy; the impact of inpatient rehabilitation on outcomes for patients with cancer; and the long-term effects of posttreatment exercise on pain in young women with breast cancer. Patient-specific cases of carcinoma of the colon in a child, managing severe radiation dermatitis after head and neck radiotherapy, striking rash in a patient on a checkpoint inhibitor, and a small gastric GIST with high mitotic index are also included. Dr Henry rounds off his comments with an examination of the challenges presented by tumor heterogeneity in the war on cancer.

Listen to the podcast below

NASHVILLE, Tenn. – Gadolinium-based contrast agents (GBCAs) are necessary for the accurate initial diagnosis of patients experiencing a first clinical attack of symptoms consistent with multiple sclerosis and for following patients with highly active disease or sudden, unexpected declines.

But according to new guidelines issued by the Consortium of Multiple Sclerosis Centers, GBCAs are optional – although helpful – in many other clinical scenarios, especially when noncontrast MRI can provide answers.

“The key is that there is an optional role for gadolinium,” David Li, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. Although a GBCA is still “essential” for some clinical scenarios in clinically isolated syndrome and MS, the new guidelines suggest that standard, high-quality MRI without contrast can adequately identify the majority of new MS lesions over time.

“But I would like to remind you that if you need to know about ongoing, current activity,” in settings of acute change, then gadolinium is still necessary, Dr. Li of the University of British Columbia, Vancouver, said in a video interview.

The guideline is an update of CMSC’s 2015 document, which endorsed a more liberal use of GBCAs. This more conservative stance reflects new research on the agents and an update in 2017 from the Food and Drug Administration that required a class-wide warning about gadolinium retention.

The agency began investigating gadolinium in 2015. In May 2017, it issued a statement confirming that gadolinium accumulates in neural tissue and can be retained for an extended period. However, in reviewing the evidence, FDA found no concerning safety signals. Despite the presumed lack of toxicity, the agency issued the warning and recommended limiting the contrast agent’s use – a move reflected in CMSC’s new MRI protocol guidelines.

“While there is no known CNS toxicity, these agents should be used judiciously, recognizing that gadolinium continues to play an invaluable role in specific circumstances related to the diagnosis and follow-up of individuals with MS,” the document notes.

[email protected]

NASHVILLE, Tenn. – Gadolinium-based contrast agents (GBCAs) are necessary for the accurate initial diagnosis of patients experiencing a first clinical attack of symptoms consistent with multiple sclerosis and for following patients with highly active disease or sudden, unexpected declines.

But according to new guidelines issued by the Consortium of Multiple Sclerosis Centers, GBCAs are optional – although helpful – in many other clinical scenarios, especially when noncontrast MRI can provide answers.

“The key is that there is an optional role for gadolinium,” David Li, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. Although a GBCA is still “essential” for some clinical scenarios in clinically isolated syndrome and MS, the new guidelines suggest that standard, high-quality MRI without contrast can adequately identify the majority of new MS lesions over time.

“But I would like to remind you that if you need to know about ongoing, current activity,” in settings of acute change, then gadolinium is still necessary, Dr. Li of the University of British Columbia, Vancouver, said in a video interview.

The guideline is an update of CMSC’s 2015 document, which endorsed a more liberal use of GBCAs. This more conservative stance reflects new research on the agents and an update in 2017 from the Food and Drug Administration that required a class-wide warning about gadolinium retention.

The agency began investigating gadolinium in 2015. In May 2017, it issued a statement confirming that gadolinium accumulates in neural tissue and can be retained for an extended period. However, in reviewing the evidence, FDA found no concerning safety signals. Despite the presumed lack of toxicity, the agency issued the warning and recommended limiting the contrast agent’s use – a move reflected in CMSC’s new MRI protocol guidelines.

“While there is no known CNS toxicity, these agents should be used judiciously, recognizing that gadolinium continues to play an invaluable role in specific circumstances related to the diagnosis and follow-up of individuals with MS,” the document notes.

[email protected]

NASHVILLE, Tenn. – Gadolinium-based contrast agents (GBCAs) are necessary for the accurate initial diagnosis of patients experiencing a first clinical attack of symptoms consistent with multiple sclerosis and for following patients with highly active disease or sudden, unexpected declines.

But according to new guidelines issued by the Consortium of Multiple Sclerosis Centers, GBCAs are optional – although helpful – in many other clinical scenarios, especially when noncontrast MRI can provide answers.

“The key is that there is an optional role for gadolinium,” David Li, MD, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. Although a GBCA is still “essential” for some clinical scenarios in clinically isolated syndrome and MS, the new guidelines suggest that standard, high-quality MRI without contrast can adequately identify the majority of new MS lesions over time.

“But I would like to remind you that if you need to know about ongoing, current activity,” in settings of acute change, then gadolinium is still necessary, Dr. Li of the University of British Columbia, Vancouver, said in a video interview.

The guideline is an update of CMSC’s 2015 document, which endorsed a more liberal use of GBCAs. This more conservative stance reflects new research on the agents and an update in 2017 from the Food and Drug Administration that required a class-wide warning about gadolinium retention.

The agency began investigating gadolinium in 2015. In May 2017, it issued a statement confirming that gadolinium accumulates in neural tissue and can be retained for an extended period. However, in reviewing the evidence, FDA found no concerning safety signals. Despite the presumed lack of toxicity, the agency issued the warning and recommended limiting the contrast agent’s use – a move reflected in CMSC’s new MRI protocol guidelines.

“While there is no known CNS toxicity, these agents should be used judiciously, recognizing that gadolinium continues to play an invaluable role in specific circumstances related to the diagnosis and follow-up of individuals with MS,” the document notes.

[email protected]

The Food and Drug Administration has approved a 2-mg dose of Olumiant (baricitinib), an orally administered Janus kinase (JAK) inhibitor, to treat adults with moderate to severe rheumatoid arthritis (RA) who have responded inadequately or poorly to methotrexate, its manufacturer, Eli Lilly, announced June 1. The regulators voted against approval of the 4-mg dose because of concerns about the safety profile.

[email protected]

The Food and Drug Administration has approved a 2-mg dose of Olumiant (baricitinib), an orally administered Janus kinase (JAK) inhibitor, to treat adults with moderate to severe rheumatoid arthritis (RA) who have responded inadequately or poorly to methotrexate, its manufacturer, Eli Lilly, announced June 1. The regulators voted against approval of the 4-mg dose because of concerns about the safety profile.

[email protected]

The Food and Drug Administration has approved a 2-mg dose of Olumiant (baricitinib), an orally administered Janus kinase (JAK) inhibitor, to treat adults with moderate to severe rheumatoid arthritis (RA) who have responded inadequately or poorly to methotrexate, its manufacturer, Eli Lilly, announced June 1. The regulators voted against approval of the 4-mg dose because of concerns about the safety profile.

[email protected]