After the 12 week treatment period, the Kupperman index for the red ginseng group significantly reduced from 18.93 to 13.32 compared with the placebo from 15.21 to 15.10. The Menopause Rating Scale score dropped significantly from 12.45 to 8.32 in the ginseng group compared with 10.23 to 9.26 in the placebo group. The hot flash score also reduced significantly in the red ginseng group.

Red ginseng also elicited a significant decrease in total cholesterol from 138.11 to 108.82 compared with the placebo, from 128.52 to 128.03. The drop in LDL was also significant in the red ginseng group compared to placebo but there were no significant differences between the two groups for HDL cholesterol or C-reactive protein. The estrogen levels were not considered to be affected by red ginseng. On the other hand, the carotid intima-media thickness was significantly reduced in the red ginseng group compared with the placebo group.

Commentary: This is not the first randomized, controlled trial using ginseng in menopause symptoms but it is the first double-blind randomized controlled trial to investigate the effect of red ginseng for 12 weeks on menopausal symptoms in postmenopausal women. In the previous trial published in 1999, there were no clear effects on hot flashes but there was an effect on quality of life. In the current study however, there was a clear effect in reducing the menopause symptoms rated on the Kupperman Index and the Menopause Rating Scale, including hot flashes. These are two of the most common research tools in evaluating menopause symptoms.

The positive results of red ginseng for hot flashes in the current study versus the negative results in the previous trial could be explained by the difference in ginseng used. Red ginseng has physiologically active components that are not present in raw white ginseng or the plain Panax ginseng. Another significant difference in the two studies is the 3gmper day of the red ginseng versus the 200 mg of ginseng in the previous study.

Reference

Young Kim S, Kyo Seo S, Mi Choi Y, et al.  Effects of red ginseng supplementation on menopausal symptoms and cardiovascular risk factors in postmenopausal women: a double-blind randomized controlled trial.  Menopause 2012;19(4):461-466

In the Nurses’ Cohort Study that followed 81,722 women from 1984 to 2010, questionnaires were assessed every 2 to 4 years. The Mediterranean diet includes a high intake of fruits, vegetables, nuts, whole grains, fish and moderate alcohol. The study found an inverse association between all 4 low-risk lifestyle factors and a lower risk of sudden cardiac death. Women at low risk for all 4 lifestyle factors had a 92% lower risk of sudden cardiac death than women at low risk for none of the lifestyle factors.

Commentary: Researchers commented that 79% of sudden cardiac death may be due to unhealthy lifestyle practices in women who do not have a diagnosis of coronary heart disease. Sudden cardiac death causes more than 50% of all the cardiac deaths and is occurs more often in women. These study results will hopefully motivate us to live healthier lifestyles.

Reference

Chiuve S, Fung T, Rexrode K, et al. Adherence to a low-risk, healthy lifestyle and risk of sudden cardiac death among women. JAMA 2011;306(1):62-69.

Approximately half of the women rarely ate chocolate and 36% ate it weekly and 17% ate it daily. Women who consumed chocolate frequently were much less likely to be hospitalized for atherosclerotic vascular disease, or even die from it, than were women who consumed chocolate rarely. Women who ate chocolate frequently were also significantly less likely to develop ischemic heart disease, congestive heart failure and plaques in the carotid artery.

Other research results and higher intake of flavonoids, including chocolate, from prior studies have also shown an association between higher chocolate intake and improved cardiovascular outcomes. Cocoa is rich in flavonoids and is the principal ingredient in cocoa. While a high quality randomized double-blind trial could confirm these observational studies… it might indeed be difficult to find women who would be willing to be in the placebo group rather than the chocolate group. For now… I encourage women to eat 1-2 oz or greater than 70% dark chocolate at least once per week; I vote for 1 oz daily!!!

Reference

Lewis J, et al. Habitual chocolate intake and vascular disease: A prospective study of clinical outcomes in older women. Arch Intern Med 2010 Nov 8; 170:1857.

The JELIS (Japan EPA Lipid Intervention Study) trial [4] included a total of 18,645 subjects (men aged 40-75 and postmenopausal women aged > 75 and a mean age of 61 years and 31% men). Those with a serum total cholesterol level of > 250 mg/dL were eligible. About 36% were hypertensive, 15% had diabetes and 20% had coronary artery disease. Subjects were randomized to pravastatin 10mg/day or simvastatin 5mg/day or the same statin doses with 1,800 mg/day of EPA. After 5 years, those in the EPA group had a 19% reduction in major cardiac events.

These three trials indicated that omega-3 PUFAs lowered the risk of CV disease in both primary and secondary prevention. While not all studies have shown favorable results, the numbers of patients treated, the doses used, and the results of the DART, GISSI and JELIS study are strong motivations to increase dietary fish intake and especially fish oil supplementation. In order to test and remove heavy metals, pesticides, other environmental contaminants and microbes, look for products that can produce independent third part testing for each lot of supplements.

Recommended doses for primary and secondary prevention:

1,000 mg/day of combined EPA/DHA

References:

[1] Harris W, Poston W, Hadock C. Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis 2007;193:1-10.

[2] Burr M, Fehily A, Gilbert J, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and Reinfarction Trial (DART). Lancet 1989;2:757-761.

[3] Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI. Lancet 2001; 357;642 and Lancet 2007;369:106 and Lancet 1999;354;447-455.

[4] Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007;369:1090-1098.

Patients were randomly assigned to drink one cup of Hibiscus or black tea two times per day for one month. Each infusion contained one tea sachet weighing 2 gm, placed in a tea pot with 240 ml boiling water and steeped for 20-30 minutes and then added one cube of sugar.

The average systolic blood pressure (SBP) in the hibiscus group decreased from 134.4 +/- 11.8 mm Hg at the start of the study to 112.7 +/- 5.7 mm Hg after 1 month. The average SBP changed from 118.6 +/-14.9 to 127.3 +/- 8.7 mm Hg in the black tea group during the same time period. There were no statistically significant effects on the mean diastolic blood pressure in either group.

Commentary:

It’s always gratifying to see a simple, safe, inexpensive herb studied for such a common problem. Hibiscus has been used historically for high blood pressure and contains several important ingredients including alkaloids, anthocyanins and quercetin. It is thought that the antioxidant and diuretic effects are the most important mechanisms.

References

Mozaffari-Khosravi H, Jalali-Khanabadi B, Afkhami-Ardekani M, et al. The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes. J Human Hypertension 2009;23:48-54.

Commentary: We know that elevated homocysteine levels are associated with the risk for AMD and B vitamins lower homocysteine levels. The current study suggests that supplementation with these three B vitamins can lower the risk for AMD, although it is not clear if this result is indeed related to homocysteine lowering or some other mechanism.

References

Christen W,et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: The women’s antioxidant and folic acid cardiovascular study. Arch Intern Med 2009. Feb 23;169:335

If you’ve not already been alarmed by the push for statins as primary heart disease prevention you will want to know that in 2006, 1.3 million coronary angioplasty procedures were done in the U.S., at a cost of $48,399.00 and 448,000 coronary bypass operations at a cost of $99,743.00. That’s a total of over 104 billion dollars. For those two procedures alone, we spent more than 100 billion dollars in 2006. If these procedures accomplished as much as they cost, that would be one thing, but even the New England Journal of Medicine reported in 2007 that angioplasties and stents do not prolong life or prevent heart attacks in stable patients; stable patients are 95% of those who undergo those procedures. And…. coronary bypass surgery sadly prolongs life in less than 3% of patients. We have good scientific evidence that diet and lifestyle changes can prevent at least 90% of all heart disease. 90%!!!!!! In yet another recent study proving this point, an intervention diet of either low-fat or Mediterranean diet significantly improved cardiovascular event free survival in those who had a previous heart attack.[1]

The well known Lyon Diet Heart Study also demonstrated a survival advantage with the Mediterranean diet.[2]

For both primary and secondary heart disease prevention, we have to step up our game in helping our patients “get religion” about rigorously changing their eating habits, losing weight, exercising a minimum of 30 minutes every day (and for overweight 40 and over women, likely 60 + minutes daily), and of course stopping smoking.

In addition to using nutritional and botanical supplementation to address any lipid or hypertension issues, a diverse approach attending to arterial health and inflammation deserves our attention as well. While questioning statins, we might also want to question our own use of nutraceuticals in treating hyperlipidemia with items such as soluble fibers, soy, red yeast rice, niacin, phytosterols, pantethine, tocotrienols, resveratrol, policosanol, gugulipids or garlic. I have as of yet not abandoned this thinking of improving lipid profiles, but a broader perspective is in order. While of course attending to normalizing blood pressure, (magnesium, potassium, bonito protein, marine omega 3 fatty acids, vitamin D, lycopene, pycnogenol, hawthorne, L-arginine, carnitine, NAC and more) I have also expanded my attention to arterial health with attention to dilatation, anti-inflammation, reduction of LDL oxidation, platelet function and reducing vascular calcification.

I look more to combination ingredients and product formulations that approach cardiovascular health from the multi-mechanism perspective. While not an exhaustive list, items to consider beyond lipid therapies:

Dilatation: L-arginine, quercitin/flavonoids, vitamin C and E, magnesium, co-enzyme Q-10, taurine, garlic, soy

Anti-inflammation: marine omega 3 fatty acids, flax oil, isoquercitin, quercitin/rutin/ flavonoids, resveratrol

Reduce LDL oxidation: niacin, green tea, garlic, pantethine, resveratrol, policosanol, Co-enzyme Q-10

Anti-thrombotic: marine omega 3 fatty acids, garlic, pomegranate, nattokinase, ginger, resveratrol

Reduce vascular calcification: Vitamin K2, marine omega 3 fatty acids

More than 500,000 women die of cardiovascular-related causes annually in the U.S., with approximately 100,000 prematurely, before the age of 65. Starting at age 50, more women die of cardiovascular diseases than of any other condition and women younger than 55 who have a heart attack have a worse prognosis and higher incidence of heart attack-related death than do men of the same age who have a heart attack, as well as a greater chance of having another heart attack. Disability due to cardiovascular disease is also a major concern, especially in older women. And for African-American women, the risk of heart-related death is even greater- it is twice as high as for Caucasian women.

To be successful with our mission of preventing and treating heart disease, and helping women with the difficult challenges of weight loss and lifestyle changes, we must enhance patient education, expand strategies for motivation, improve and broaden plant/nutrient based supplementation prescribing, and continue wise and considered selective/judicious use of pharmaceutical/conventional interventions.

References

[2] De Lorgeril M, Salen P, Martin J, et al. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 1999;99:779-785.

The results of this study suggest that a moderate to severe vitamin D deficiency is a risk factor for developing cardiovascular disease.  One would hope that treatment of vitamin D deficiency with vitamin D supplementation or adequate exposure to sunlight could reduce that risk.  While a randomized intervention trial would be needed to assess vitamin D supplementation as a treatment strategy, we do have other positive evidence showing vitamin D supplementation reducing blood pressure, ventricular hypertrophy and inflammatory cytokines.
References

Want T, Pencina M, Booth S, et al.  Vitamin D deficiency and risk of cardiovascular disease.  Circulation. 2008; 117: 503-511.

Isoflavones derived from Trifolium pratense had a beneficial effect on the lipid profile of postmenopausal women with a BMI > 25. There was also a significant decrease in TC ( 4.6%) LDL-C (15.6%) and LpA levels  (63.8%) in those that received the red clover isoflavones.

Commentary

At least five previously published reports of T. pratense isoflavones on lipid profiles in men and premenopausal and postmenopausal women have been positive, and at least two have shown no effect. This is the first published report on postmenopausal women with an increased BMI using T. pratense isoflavones to lower lipids. These decreases in TC, LDL-C and LpA correlate with findings that support a meaningful reduction in cardiovascular risk, and even more so in postmenopausal women with high lipid values. This study is promising and provides another important lifestyle supplemental tool for women who do not want to use or may not be good candidates for hormonal or statin therapies to lower their risk of cardiovascular disease.

References

• Chedraui P, San Miguel G, Hidalgo L, et al. Effect of Trifolium pratense-derived isoflavones on the lipid profile of postmenopausal women with increased body mass index. Gynecological Endocrinology 2008;24(11):620-624.

Bolland M, Barber P, Doughty R, et al. Vascular events in healthy older women receiving calcium supplementation: Randomised controlled trial. BMJ 2008;Feb 2; 336:262-266

[Click here to download fulltext PDF from BMJ]

Commentary: It is interesting and important to point out that the Women’s Health Initiative ( Circulation 2007;115:846) showed no statistically significant increase in cardiovascular events in postmenopausal women receiving calcium supplements and another study showed a non-significant but yet a trend in increased risk for ischemic heart disease. (Arch Intern Med 2006;166:869). These three studies all point to the fact that there is no definite statement or conclusion that can be made regarding calcium and cardiovascular events. That said, I am concerned that the importance of calcium supplementation in postmenopausal women, especially younger postmenopausal women, is very overplayed. And, most individuals do not estimate their dietary calcium sources, and then use a pill to supplement in addition to dietary sources to meet a total of 1,200mg-1,500 mg per day. Rather, they often take 1,000 mg to 1,500 mg per day, in addition to their dietary sources. A result of this misinterpretation of calcium guidelines might be excessive calcium and depletion of other nutrients such as copper, silicon and magnesium, all of which have cardioprotective benefits. In addition, these total daily calcium guidelines turn out to be most important to young girls and postmenopausal women 65 and older. These are the times in life when lack of bone architecture/density growth (young girls) and bone loss (elderly women) is most crucial in the prevention of osteoporosis and risk for fractures. For women in their 30’s, 40’s, 50’s and early 60’s, our bones seem to do just fine with average dietary intake.