Editor's Note: In this second column in the recently engaged JACM partnership with the Cochrane Complementary Medicine Field, Co-Director of the Field L. Susan Wieland, PhD, shares synopses of eight Cochrane systematic reviews on topics deemed of particular interest to those in the integrative health and medicine fields. Wieland chose to call attention to interventions such as the quite topical vitamin D and COVID-19, the long-standing claims related to ginseng and erective dysfunction, traditional Chinese medicine for certain populations with polycystic ovarian syndrome, examination of lifestyle advice interventions on infertility, and more. JACM is pleased to play this ongoing role in the dissemination of these reviews.—John Weeks, Contributing Editor, Special Projects and Collaborations, JACM (johnweeks-integrator.com).
Chinese Herbal Medicine for Subfertile Women with Polycystic Ovarian Syndrome
Citation: Zhou K, Zhang J, Xu L, Lim CE. Chinese herbal medicine for subfertile women with polycystic ovarian syndrome. Cochrane Database of Systematic Reviews 2021, Issue 6. Art. No.: CD007535. DOI: 10.1002/14651858.CD007535.pub4
Polycystic ovarian syndrome (PCOS), a condition in which the ovaries are enlarged and the body produces high levels of androgens and insulin and lower levels of progesterone, can make it difficult for women to become pregnant. Treatment usually consists of lifestyle changes, hormonal medications, and metformin for insulin resistance. Follicle aspiration and ovulation induction (FAO) or laparoscopic ovarian drilling (LOD) is sometimes used to help women with PCOS conceive. Chinese herbal medicine (CHM) has also been used to treat subfertility in PCOS and this Cochrane review looked at the safety and effectiveness of CHM, alone or in combination with other treatments, for improving fertility in women with PCOS.
The authors found eight studies with 609 participants in which CHM was compared with clomiphene, CHM plus clomiphene was compared with clomiphene alone, CHM plus FAO was compared with FAO alone, and CHM plus LOD was compared with LOD alone. The studies reported on pregnancy rates but there was no information on live births. The authors found limited evidence that adding CHM to clomiphene may improve chances of pregnancy. However, the authors concluded that there was not yet sufficient evidence to be certain about the effectiveness or safety of CHM for fertility in PCOS. There is a need for further good-quality trials reporting on live birth outcomes and adverse events.
Vitamin D Supplementation for the Treatment of COVID-19: A Living Systematic Review
Citation: Stroehlein JK, Wallqvist J, Iannizzi C, Mikolajewska A, Metzendorf M-I, Benstoem C, Meybohm P, Becker M, Skoetz N, Stegemann M, Piechotta V. Vitamin D supplementation for the treatment of COVID-19: a living systematic review. Cochrane Database of Systematic Reviews 2021, Issue 5. Art. No.: CD015043. DOI: 10.1002/14651858.CD015043
There is an association between low blood levels of vitamin D and an increased risk of severe acute respiratory syndrome coronavirus-2 positivity, severe COVID-19 disease, and COVID-19 mortality. This Cochrane review was conducted to evaluate the randomized trial evidence on vitamin D as a treatment for COVID-19.
The authors found one small trial (n = 40) of vitamin D versus placebo in persons with asymptomatic or mild COVID-19. The trial reported that persons receiving vitamin D had increased blood levels of vitamin D after treatment but did not report on all-cause mortality or other clinical outcomes, including adverse events. The authors could not make any conclusions about the effectiveness or safety of vitamin D as a treatment for mild or asymptomatic COVID-19.
The authors found two trials with a total of 316 participants testing vitamin D as a treatment for persons hospitalized with moderate or severe COVID-19. The two trials differed in populations, comparators, and treatments, and the authors could not combine the trials for analysis even when the outcomes were similar. For example, although each trial had information on all-cause mortality, the results were inconsistent between trials and the authors concluded that the evidence was very uncertain. Other outcomes were also either unavailable or the quantity and quality of the information were inadequate.
The authors stated that there is currently insufficient good-quality evidence to inform the use of vitamin D for COVID-19. However, they are aware of multiple trials on vitamin D for COVID-19 that are either still in progress or not yet published. This review will be continuously updated with information from these trials, and an update will be published as soon as the conclusions of the review provide more insight into the effectiveness or safety of vitamin D as a treatment for COVID-19.
Ginseng for Erectile Dysfunction
Citation: Lee HW, Lee MS, Kim T-H, Alraek T, Zaslawski C, Kim JW, Moon DG. Ginseng for erectile dysfunction. Cochrane Database of Systematic Reviews 2021, Issue 4. Art. No.: CD012654. DOI: 10.1002/14651858.CD012654.pub2
Erectile dysfunction is the ongoing inability to get and keep an erection firm enough for sexual intercourse. The condition can be very distressing and increases in prevalence with age. Common treatments include phosphodiesterase inhibitors such as avanafil or sildenafil, and these medications are helpful for many but not all men. Ginseng has traditionally been used as an herbal remedy for male reproductive and sexual function, and this Cochrane review, therefore, looked at the evidence on the safety and effectiveness of ginseng in treating erectile dysfunction.
The authors found a total of nine studies with 587 participants in which ginseng was compared with placebo for treating erectile dysfunction. No studies comparing ginseng with conventional treatment or comparing ginseng plus conventional treatment with conventional treatment alone were found. The authors concluded that while ginseng may slightly improve the self-reported ability to have sexual intercourse, the effect is negligible when measured on validated questionnaires. There may be little or no difference between ginseng and placebo in the rate of adverse events, however, the studies were 4–12 weeks in duration and there was no information on long-term use. Because the certainty of the available evidence is low, additional well-conducted studies may further clarify the safety and effectiveness of ginseng for erectile dysfunction.
Probiotics for Preventing Gestational Diabetes
Citation: Davidson SJ, Barrett HL, Price SA, Callaway LK, Dekker Nitert M. Probiotics for preventing gestational diabetes. Cochrane Database of Systematic Reviews 2021, Issue 4. Art. No.: CD009951. DOI: 10.1002/14651858.CD009951.pub3
Gestational diabetes mellitus (GDM) is when diabetes develops during pregnancy. GDM may increase the risk of developing high blood pressure and protein in the urine (preeclampsia) during pregnancy, which is dangerous for both the mother and the baby. Furthermore, although blood sugar levels usually return to normal after delivery, GDM increases a woman's risk of later developing type 2 diabetes. Both lifestyle interventions and dietary supplements have been used in an attempt to reduce the risk of developing GDM. This updated Cochrane review was conducted to evaluate the safety and effectiveness of probiotics for preventing GDM.
The authors found a total of seven studies with 1647 participants. Based on six studies with variable findings, the authors concluded that it is unclear whether probiotics affect the risk of developing GDM. There was no information available from the studies on the risk of later developing type 2 diabetes. However, the authors found convincing evidence that the risk of preeclampsia is increased in women who take probiotics compared with placebo. Several ongoing studies will provide more information on the potential benefits and risks of probiotics for prevention of GDM in different subpopulations. In the meantime, the authors advise pregnant women to be cautious about the use of probiotics.
Preconception Lifestyle Advice for People with Infertility
Citation: Boedt T, Vanhove A-C, Vercoe MA, Matthys C, Dancet E, Lie Fong S. Preconception lifestyle advice for people with infertility. Cochrane Database of Systematic Reviews 2021, Issue 4. Art. No.: CD008189. DOI: 10.1002/14651858.CD008189.pub3
When women experience infertility, they may be advised to change some lifestyle factors to improve their chances of conceiving. The factors may include diet, exercise, and alcohol intake, among others. This Cochrane review sought to assess what lifestyle advice during or before fertility treatment might lead to increased chances of conceiving and having a baby.
The authors found seven randomized controlled trials with 2130 participants; six trials included only women and one trial included women and their male partners. Three trials compared advice on multiple lifestyle topics with no lifestyle advice, two trials looked at advice on weight loss for women with obesity, one trial looked at advice on reducing alcohol intake for women with at-risk alcohol drinking, and one trial looked at advice on smoking cessation in women who smoke. Based on a single study (n = 626) comparing advice on a combination of topics with no lifestyle advice, the authors concluded that lifestyle advice on a combination of topics may have little or no effect on the number of live births. The evidence on pregnancies and births for advice on weight loss, alcohol reduction, and smoking cessation topics was either not available or uncertain because of problems with study methods and small sample sizes. The authors identified nine ongoing studies that may provide more evidence.
Approaches for Discontinuation Versus Continuation of Long-Term Antidepressant Use for Depressive and Anxiety Disorders in Adults
Citation: Van Leeuwen E, van Driel ML, Horowitz MA, Kendrick T, Donald M, De Sutter AIM, Robertson L, Christiaens T. Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. Cochrane Database of Systematic Reviews 2021, Issue 4. Art. No.: CD013495. DOI: 10.1002/14651858.CD013495.pub2
People may successfully use antidepressants to treat depression or anxiety but wish to stop using them when they are no longer experiencing symptoms. However, discontinuing antidepressants may lead to withdrawal symptoms or to relapse, and it is not clear what methods might lead to successful discontinuation. This Cochrane review summarized the evidence on different approaches to discontinuation compared with continuation for people taking antidepressants for at least 6 months.
The authors found 33 randomized controlled trials with 4995 participants, mostly carried out in participants with at least two previous depression episodes being treated by mental health specialists. Some studies had multiple comparisons. Overall, 13 studies looked at abrupt discontinuation, 18 studies looked at tapering treatment for at least a week (usually 4 weeks or less), 4 studies looked at providing psychological support with discontinuation, and 1 study looked at providing a patient-specific letter to general practitioners suggesting discontinuation be considered.
Both abrupt discontinuation and tapering may increase the risk of relapse, but the authors stated that conclusions about both relapse and withdrawal symptoms are very uncertain. There was no information on successful discontinuation. Psychological support with discontinuation may result in successful discontinuation rates of 40%–75% and there may be little or no effect on rates of relapse. For the letter to general practitioners, there may be little or no effect on successful discontinuation or relapse, and data on withdrawal symptoms were not reported. The authors noted that studies rarely report rates of successful discontinuation, do not examine tapering schemes longer than 1 month, do not sufficiently distinguish between withdrawal symptoms and relapse, and do not include populations with no or one previous episode of illness. Because of these gaps and the uncertainty of the evidence, further studies are likely to change the conclusions of this review.
Interventions for Reducing Sedentary Behavior in Community-Dwelling Older Adults
Citation: Chastin S, Gardiner PA, Harvey JA, Leask CF, Jerez-Roig J, Rosenberg D, Ashe MC, Helbostad JL, Skelton DA. Interventions for reducing sedentary behaviour in community-dwelling older adults. Cochrane Database of Systematic Reviews 2021, Issue 6. Art. No.: CD012784. DOI: 10.1002/14651858.CD012784.pub2
Sedentary behavior in the elderly is associated with an increased risk of frailty, functional decline, and premature mortality, and it is thought that reducing sedentary time may improve health and well-being. This Cochrane review summarized the evidence on the effects of interventions to reduce sedentary behavior among community-dwelling adults of age 60 years or more.
The authors found seven randomized controlled trials with 397 participants, who were mostly white, female, relatively young, and well educated. The interventions were individual level and included counseling, information sessions or workshops, prompts, and feedback. Interventions were compared with no intervention or with an intervention that did not focus on sedentary behavior. The authors concluded that the interventions may reduce sedentary time, but their certainty about this is low. It is also unclear whether the interventions impact physical fitness, body composition, blood pressure, or blood markers of cardiometabolic health, and there was little or no information on depression, quality of life, cost-effectiveness, and adverse effects. The authors noted that studies did not aim at restructuring environments, changing policies, or altering cultural and social norms, and that the evidence is limited to interventions aimed at changing psychology and behavior. The studies were also all conducted in high-income countries, which limits the generalizability to other contexts. Because of small sample sizes and inconsistencies in some results between individual studies, the overall certainty of the conclusions is low to very low. Future studies are needed to clarify or change the current findings, and to provide additional information on populations, interventions, and outcomes not covered in current studies.
Altered Dietary Salt Intake for People with Chronic Kidney Disease
Citation: McMahon EJ, Campbell KL, Bauer JD, Mudge DW, Kelly JT. Altered dietary salt intake for people with chronic kidney disease. Cochrane Database of Systematic Reviews 2021, Issue 6. Art. No.: CD010070. DOI: 10.1002/14651858.CD010070.pub3
High salt intake is common among people with chronic kidney disease (CKD), and reducing this intake may reduce the risk of developing heart disease and delay the progression of kidney disease. This Cochrane review summarized the most recent evidence on the potential benefits and harms of interventions to reduce dietary salt among people with CKD.
The authors found 21 cross-over or parallel randomized controlled trials with 1197 participants. Twelve trials were in people in the earlier stages of kidney disease (before dialysis). Nine trials were in people with end-stage kidney disease (ESKD): seven trials in people on dialysis and two trials in people post-transplant. The studies ranged in duration from 1 to 36 weeks and were too brief to detect effects on clinical events such as development of heart disease or progression to ESKD.
The authors found that reducing salt intake reduced both systolic and diastolic blood pressure in all groups of patients. Reducing salt by ∼1690 mg sodium/day lowered systolic blood pressure by a mean of 7 mg Hg and diastolic blood pressure by a mean of 4 mg Hg. Reducing dietary salt also reduced 24-h urinary protein excretion by 34% and reduced 24-h urinary albumin excretion by 36%, however, most of this information was available from trials in people at earlier stages of CKD. With regard to risks, reducing salt intake probably leads to an increased risk of symptomatic hypotension, but there is little information on other adverse events. The authors suggested that although there is no research into the long-term effects of reducing dietary salt in CKD, if the effects in these studies are maintained over the long term, this could translate into clinical benefits such as slowed progression of kidney disease and reduced risk of cardiovascular events and death.