Joel Evans, MD discusses research studies on topics such as garlic use and blood pressure, therapeutic approaches on uterine artery blood flow and dietary fiber intake in pregnancy.

by Joel M. Evans, MD

Effect of garlic on blood pressure: a systematic review and meta-analysis.

Ried et al., BMC Cardiovasc Disord. 2008 Jun 16;8:13.

BACKGROUND: Non-pharmacological treatment options for hypertension have the potential to reduce the risk of cardiovascular disease at a population level. Animal studies have suggested that garlic reduces blood pressure, but primary studies in humans and non-systematic reviews have reported mixed results. With interest in complementary medicine for hypertension increasing, it is timely to update a systematic review and meta-analysis from 1994 of studies investigating the effect of garlic preparations on blood pressure. METHODS: We searched the Medline and Embase databases for studies published between 1955 and October 2007. Randomised controlled trials with true placebo groups, using garlic-only preparations, and reporting mean systolic and/or diastolic blood pressure (SBP/DBP) and standard deviations were included in the meta-analysis. We also conducted subgroup meta-analysis by baseline blood pressure (hypertensive/normotensive), for the first time. Meta-regression analysis was performed to test the associations between blood pressure outcomes and duration of treatment, dosage, and blood pressure at start of treatment. RESULTS: Eleven of 25 studies included in the systematic review were suitable for meta-analysis. Meta-analysis of all studies showed a mean decrease of 4.6 +/- 2.8 mm Hg for SBP in the garlic group compared to placebo (n = 10; p = 0.001), while the mean decrease in the hypertensive subgroup was 8.4 +/- 2.8 mm Hg for SBP (n = 4; p < 0.001), and 7.3 +/- 1.5 mm Hg for DBP (n = 3; p < 0.001). Regression analysis revealed a significant association between blood pressure at the start of the intervention and the level of blood pressure reduction (SBP: R = 0.057; p = 0.03; DBP: R = -0.315; p = 0.02). CONCLUSION: Our meta-analysis suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension.

My Comment:

This is an important article because it brings garlic back into the consciousness of the integrative health practitioner. Garlic, a long used natural intervention for cardiovascular and immune health, seems to have lost its luster in the natural pharmacopeia due to a NCCAM funded study published in the Archives of Internal Medicine in 2007 that failed to show effectiveness in lowering cholesterol (Gardner et al., Effect of raw garlic vs commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia: a randomized clinical trial. Arch Intern Med. 2007 Feb 26;167(4):346-53.). However, there were some serious flaws in that study, such as a lack of control for diet in study and placebo groups and the fact that oxidized LDL, the atherogenic form of LDL, was not studied. The diet issue is important because as the study was conducted, it is impossible to know if the diets in the two groups were the same, and how can you judge the effectiveness of a lipid lowering agent if people eat a high fat diet?

It is that Ried et al. published this article after the Gardner et al. article that makes it so important, for it is far too easy to let a single negative study erase the positives of successful historical and clinical use as well as previous positive studies. I just explained why I do not believe the Gardner et al. paper definitively shows that garlic has no beneficial effects on atherogenesis, it is important to realize that the way natural medicines are used are often for broad effects on different systems of the body. Garlic, for example, is used for cardiovascular health, not just to improve the lipid profile. As such, the paper by Ried et al addresses another important component of cardiovascular health: blood pressure. They performed an extensive literature review and meta-analysis and found that there was justification in the literature to state that garlic does reduce systolic blood pressure in people with hypertension.

As with any intervention, there are precautions to remember. Garlic supplements must be used carefully or not at all in patients on any blood thinning medications and patients having surgery should stop garlic supplementation 1-2 weeks prior to surgery. Finally, a little known but important fact about garlic is that it has been found to interfere with the effectiveness of saquinavir, a drug used to treat HIV infection.

In conclusion, I think that garlic is a gentle and safe (see caveats above) intervention that offers enough promise to justify its status as a therapy for the integrative clinician. Certainly a first step is to encourage the use of garlic in the diet and then consider supplementing with a garlic nutraceutical for cardiovascular health in your patients in the context of an “experiment”, where blood pressure and lipid profiles are followed. In that way both the clinician and patient can make an informed decision about continuing the supplement after just 3 months.

Prevention of acute radiation-induced esophagitis with glutamine in non-small cell lung cancer patients treated with radiotherapy: Evaluation of clinical and dosimetric parameters.

Topkan et al., Lung Cancer. 2008 Aug 6. [Epub ahead of print] PMID: 18691789

BACKGROUND: The purpose of this study was to evaluate the efficacy of oral glutamine in the prevention of acute radiation-induced esophagitis (ARIE) and weight loss in lung carcinoma patients, and to determine the clinical/dosimetric predictors of ARIE. PATIENTS AND METHODS: Data from 41 patients with stage III lung carcinoma treated with thoracic irradiation were retrospectively analyzed. Twenty-two patients (53.6%) received prophylactic powdered glutamine in doses of 10g/8h. Prescribed radiation dose to planning target volume was 60Gy, in 30 fractions, 5 days/week. The primary endpoint included the ARIE incidence and its correlation with clinical/dosimetric factors relative to treatment with glutamine. RESULTS: Glutamine was well tolerated. Grade 2 or 3 ARIE occurred in 20 (48.8%) of 41 patients: seven in the glutamine-supplemented group, and 13 in the glutamine-free group (p=0.002). All seven patients with grade 3 esophagitis were in the glutamine-free group (36.8% vs. 0%). Glutamine supplementation appeared to significantly delay ARIE onset for six days (22 days vs. 16 days; p=0.002). Glutamine-supplemented patients demonstrated a lower incidence of grade 2 or 3 ARIE (27.2%), and gained weight during radiotherapy (p=0.04). V55 was the only dosimetric parameter that correlated with the severity of ARIE in glutamine-free patients: a V55 of <35% had a 31% risk of ARIE grade 2 or 3, and the risk increased to 76% with a V55 of >/=35% (p=0.01). CONCLUSION: This schedule and dosage of glutamine may be beneficial in the prevention of ARIE and weight loss in lung cancer patients undergoing thoracic irradiation.

My Comment: 

Integrative practitioners are all aware of the profound healing effects of glutamine on the gut mucosa, recommending it for inflammatory bowel disease, leaky gut, irritable bowel and colon cancer protection among others. What is sometimes overlooked is the protection that glutamine offers on the upper GI tract. For example, it is a well described treatment for the oral ulcers that often accompany anthracycline chemotherapy, and some oncology centers now administer glutamine routinely with chemotherapy for stomatitis prevention. Other published positive effects of glutamine on cancer treatment include increasing the selectivity of chemotherapy so that it attacks only the cancer cells while sparing healthy cells (Rouse et al., Ann Surg. 1995 April; 221(4): 420–426) and as a treatment/preventive for peripheral neuropathy (Vahdat et al., Clin Cancer Res. 2001 May;7(5):1192-7).

This study is important two reasons, first because it reminds us that glutamine is important for the health if the upper GU tract and second, because it shows us that glutamine’s effectiveness in oncologic treatment involves radiation as well as chemotherapy.  The statistically significant benefits of glutamine to significantly delay the onset of esophagitis for six days as well as decrease its incidence are also clinically significant. More studies are forthcoming, but for now glutamine is an important and safe adjunct to cancer treatment.

Low-dose aspirin and omega-3 fatty acids improve uterine artery blood flow velocity in women with recurrent miscarriage due to impaired uterine perfusion.

Lazzarin et al., Fertil Steril. 2008 Aug 8. [Epub ahead of print] PMID: 18692841

Objective: To determine the effect of different therapeutic approaches on uterine artery blood flow in women with recurrent miscarriage (RM) and impaired uterine perfusion.

Design: Prospective, randomized study.

Setting: Department of Obstetrics and Gynecology, University of Rome ‘‘Tor Vergata,’’ Italy.

Patient(s): Sixty women with unexplained RM and impaired uterine perfusion.

Intervention(s): Patients were randomly assigned to three different therapeutic regimens: 20 patients receiveda daily dose of 100 mg of aspirin (LDA); 20 patients were treated with omega-3 fatty acids (U3), 4 g daily; and 20 patients received LDA plus U3.

Main Outcome Measure(s): Doppler measurement of uterine artery pulsatility index (PI) was performed, in the midluteal phase of the cycle, before and after 2 months of therapy.

Result(s): All therapeutic regimens induced an improvement in uterine perfusion with a significant reduction of uterine artery PI values. LDA alone or in combination with U3 was found to achieve the highest improvement of uterine blood flow. Omega-3 supplementation was less effective, as reflected by the lower PI values.

Conclusion(s): LDA and U3 are effective in improving uterine artery blood flow velocity in women with RM due to abnormal uterine perfusion. Further studies are needed to determine whether the improvement of uterine perfusion may lead to a better pregnancy outcome.

My Comment:

This is an important article because it discusses recurrent pregnancy loss, a topic that frustrates many practitioners, both conventional and integrative, and their patients. Though this article found that fish oil and aspirin were effective in improving uterine artery blood flow in patients with both impaired uterine artery blood flow and recurrent miscarriage, it remains to be proven that restoring the blood flow to the uterus will actually prevent pregnancy loss. However, because we have so little to offer these patients in proven therapies, it makes sense to try fish oil and aspirin as they are promising interventions that are safe. Of course, since recurrent pregnancy loss is such an emotionally difficult process to endure, a conventional evaluation by a specialist is recommended in case a treatable cause exists. However, in cases where no treatable cause is identified, this article gives scientific support for an empiric trial of aspirin and fish oil in this group of patients.

Dietary fiber intake in early pregnancy and risk of subsequent preeclampsia.

Qiu et al., Am J Hypertens. 2008 Aug;21(8):903-9. Epub 2008 Jul 17 PMID: 18636070

Background: Substantial epidemiological evidence documents diverse health benefits, including reduced risks of hypertension, associated with diets high in fiber. Few studies, however, have investigated the extent to which dietary fiber intake in early pregnancy is associated with reductions in preeclampsia risk. We assessed the relationship between maternal dietary fiber intake in early pregnancy and risk of preeclampsia. We also evaluated cross-sectional associations of maternal early pregnancy plasma lipid and lipoprotein concentrations with fiber intake. Methods: The study population comprised 1,538 pregnant Washington State residents. A 121-item food frequency questionnaire (FFQ) was used to assess maternal dietary intake, 3 months before and during early pregnancy; and generalized linear regression procedures were used to derive relative risk (RR) and 95% confidence intervals (CIs). Results: Dietary total fiber intake was associated with reduced preeclampsia risk. After adjusting for confounders, the RR of preeclampsia for women in the highest (>/=21.2 g/day) vs. the lowest quartile (<11.9 g/day) was 0.28 (95% CI = 0.11-0.75). We observed associations of similar magnitude when the highest vs. the lowest quartiles of water-soluble fiber (RR = 0.30; 95% CI = 0.11-0.86) and insoluble fiber (RR = 0.35; 95% CI = 0.14-0.87) were evaluated. Mean triglyceride concentrations were lower (-11.9 mg/dl, P = 0.02) and high-density lipoprotein cholesterol concentrations were higher (+2.63 mg/dl, P = 0.09) for women in the highest quartile vs. those in the lowest quartile. Conclusions: These findings of reduced preeclampsia risk with higher total fiber intake corroborate an earlier report; and expand the literature by providing evidence, which suggests that dietary fiber may attenuate pregnancy-associated dyslipidemia, an important clinical characteristic of preeclampsia.

My Comment:

Preeclampsia remains a major cause of pregnancy related morbidity and mortality for both mother and baby, so the importance of natural and safe interventions to reduce its incidence or severity cannot be understated. In this paper, Qiu et al discuss the relationship of maternal dietary fiber intake (from 3 months before conception to the end of the first trimester) and the risk of preeclampsia. A secondary objective was to evaluate the influence of dietary fiber intake on maternal plasma lipid and lipoprotein concentrations. This is important because pregnancy associated hyperlipidemia is associated with preeclampsia.

The study’s finding, that preeclampsia is by reduced by 72% in women that have the highest fiber intake compared to women with the lowest fiber intake, is an important contribution to the literature. However, whether the incidence of preeclampsia can be reduced by increasing dietary fiber in women past the first trimester of pregnancy remains to be determined. For now, this study clearly gives practitioners the scientific basis for increasing dietary fiber to 22 grams per day in women that are considering pregnancy or in the first trimester. In addition to hopefully reducing the incidence of preeclampsia, the high fiber diet will improve the lipid profile, and important benefit for those interested in the health of their female patients.

Joel M. Evans, MD is Assistant Clinical Professor of Obstetrics, Gynecology and Women’s Health at Albert Einstein College of Medicine, Founder and Director, The Center for Women’s Health in Stamford, CT and author of The Whole Pregnancy Handbook (Gotham 2005).

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