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Accepted on April 8, 2010

Red and Processed Meat Consumption and Risk of Incident Coronary Heart Disease, Stroke, and Diabetes Mellitus. A Systematic Review and Meta-Analysis

Renata Micha RD, PhD*, Sarah K. Wallace BA, and Dariush Mozaffarian MD, DrPH

From the Department of Epidemiology (R.M., S.K.W., D.M.), Harvard School of Public Health, and Division of Cardiovascular Medicine and Channing Laboratory (D.M.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.

* To whom correspondence should be addressed. E-mail: rmicha@hsph.harvard.edu .

Background—Meat consumption is inconsistently associated with development of coronary heart disease (CHD), stroke, and diabetes mellitus, limiting quantitative recommendations for consumption levels. Effects of meat intake on these different outcomes, as well as of red versus processed meat, may also vary.

Methods and Results—We performed a systematic review and meta-analysis of evidence for relationships of red (unprocessed), processed, and total meat consumption with incident CHD, stroke, and diabetes mellitus. We searched for any cohort study, case-control study, or randomized trial that assessed these exposures and outcomes in generally healthy adults. Of 1598 identified abstracts, 20 studies met inclusion criteria, including 17 prospective cohorts and 3 case-control studies. All data were abstracted independently in duplicate. Random-effects generalized least squares models for trend estimation were used to derive pooled dose-response estimates. The 20 studies included 1 218 380 individuals and 23 889 CHD, 2280 stroke, and 10 797 diabetes mellitus cases. Red meat intake was not associated with CHD (n=4 studies; relative risk per 100-g serving per day=1.00; 95% confidence interval, 0.81 to 1.23; P for heterogeneity=0.36) or diabetes mellitus (n=5; relative risk=1.16; 95% confidence interval, 0.92 to 1.46; P=0.25). Conversely, processed meat intake was associated with 42% higher risk of CHD (n=5; relative risk per 50-g serving per day=1.42; 95% confidence interval, 1.07 to 1.89; P=0.04) and 19% higher risk of diabetes mellitus (n=7; relative risk=1.19; 95% confidence interval, 1.11 to 1.27; P<0.001). Associations were intermediate for total meat intake. Consumption of red and processed meat were not associated with stroke, but only 3 studies evaluated these relationships.

Conclusions—Consumption of processed meats, but not red meats, is associated with higher incidence of CHD and diabetes mellitus. These results highlight the need for better understanding of potential mechanisms of effects and for particular focus on processed meats for dietary and policy recommendations.

Study Highlights

In this large prospective cohort study, dairy food and calcium intakes in relationship to total cancer as well as cancer at individual sites were examined in the National Institutes of Health-AARP Diet and Health Study.

In 1995 and 1996, intakes of dairy food and calcium from foods and supplements were assessed with a baseline food frequency questionnaire.

Demographic characteristics were also assessed with the baseline questionnaire. Compared with participants in the lowest quintile of dairy food or total calcium intake, participants in the highest quintile were more likely to be white, non-Hispanic; college educated; physically active; current menopausal hormone therapy users if female, and to have a lower body mass index, but they were less likely to smoke cigarettes and to drink alcohol,

During follow-up from 1995 to 2003, incident cancer cases were identified through linkage with state cancer registries.

A Cox proportional hazard model was used to estimate relative risks and 2-sided 95% CIs.

During an average of 7 years of follow-up, 36,965 and 16,605 cancer cases were identified in men and women, respectively.

Results demonstrated that total calcium intake was not related to total cancer in men but was nonlinearly associated with total cancer in women: the risk decreased with total calcium intake up to approximately 1300 mg/day, above which no further risk reduction was observed.

In addition, dairy food and dietary, supplemental, and total calcium intakes were not associated with total cancer mortality rates in both men and women.

In both men and women, dairy food and calcium intakes were inversely associated with cancers of the digestive system (multivariate relative risk for the highest quintile of total calcium vs the lowest, 0.84; 95% CI, 0.77 - 0.92 in men and 0.77; 95% CI, 0.69 - 0.91 in women), especially with colorectal cancer.

Supplemental calcium intake was also inversely associated with colorectal cancer risk.

Calcium intake was not related to breast, endometrial, ovarian, or prostate cancer.

Limitations to this study were that there was lack of evaluation for associations with intakes of dairy food and calcium on tumor subtype or tumor aggressiveness of site-specific cancers; residual confounding by unknown or unmeasured risk factors may exist for some cancers; in the analysis of low-incidence cancers, there was limited statistical power to examine an association; and because the diet was only assessed at baseline, it may not account for long-term usual intake as accurately as repeated measurements of diet during follow-up.

Pearls

Current dietary guidelines recommend 1200 mg/day of calcium for adults 50 years and older and 3 cups per day of fat-free or low-fat dairy food according to the Institute of Medicine and the 2005 dietary guidelines for Americans, respectively.

Calcium intake is associated with a lower risk for total cancer in women and cancers of the digestive system, especially colorectal cancer, in both men and women.

By CHERYL WITTENAUER, Associated Press Writer Wed Jun 27, 7:20 PM ET

ST. LOUIS - Most women know that calcium is critical in preventing osteoporosis, the disease of progressive bone loss and fractures that affects millions of Americans.

But which source is better — calcium-rich foods or supplements? A preliminary study by researchers at Washington University School of Medicine suggests dietary calcium may be better at protecting bone health.

Though not definitive, the study found that women who get most of their daily calcium from food have healthier bones and higher bone density than women whose calcium comes mainly from supplemental tablets.

That was true even though the supplement-takers had higher average levels of calcium.

Calcium from dietary sources is generally better absorbed than that from supplements, which could help explain the difference, said the study's lead author, Dr. Reina Armamento-Villareal.

Those getting calcium from foods also had more estrogen in their bodies; the hormone is needed to maintain bone mineral density. Researchers can't yet explain the food-estrogen connection.

The research is preliminary and offers "a springboard to do something more, a hypothesis to test," said Armamento-Villareal, a bone specialist and assistant professor in the School of Medicine's division of bone and mineral diseases. It was published in the May issue of the American Journal of Clinical Nutrition.

Researchers asked 183 postmenopausal women to meticulously document their diet and their calcium supplement intake for seven days. They tested their bone mineral density and their urine for levels of estrogen.

The women then were divided into three groups: those who got at least 70 percent of their daily calcium from supplements, those who got the same amount from dairy products and other food, and those whose calcium-source percentages fell somewhere in between.

The "diet group" took in the least calcium, an average of 830 milligrams per day. Yet, the group had higher bone density in their spines and hip bones than women in the "supplement group," who consumed 1,030 milligrams per day.

Women in the "diet plus supplement group" tended to have the highest bone mineral density as well as the highest calcium intake at 1,620 milligrams per day.

An analysis showed that women in the "diet group" and the "diet plus supplement group" had higher levels of estrogen, needed for bone mineral density.

Dr. Robert Recker, who heads osteoporosis research at the Creighton University School of Medicine in Omaha, noted weaknesses in the study, which he said "is certainly not definitive."

Those who got calcium from their diet might have also taken in more vitamin D from milk, which would aid in calcium absorption. As for the estrogen connection, they might have eaten plant sources containing more of the hormone, he said.

"Nevertheless it's not to be ignored," Recker said. "Observation studies are very good for generating a hypothesis to be tested later in an outright experiment."

Dairy foods and calcium-fortified orange juice are excellent sources of calcium. Dark green, leafy vegetables also contain it, though it is not as readily absorbed as calcium from dairy, researchers said.

Armamento said she'd like to do a long-term study of teenagers whose bones are still developing to see what, if any, differences might emerge among young women taking calcium from diet versus supplements.

"It's a lifestyle issue," she said, noting that some teenagers avoid dairy products.

By Bill BerkrotSat Mar 24, 5:59 PM ET

Chocoholics were given further reason to rejoice on Saturday when a small clinical study showed that dark chocolate improves the function of blood vessels.

While the researchers cautioned against bingeing on bon bons, they said the findings of the trial were clear and called for larger such studies to confirm the results.

"In this sample of healthy adults, dark chocolate ingestion over a short period of time was shown to significantly improve (blood vessel) function," said Dr. Valentine Yanchou Njike of Yale Prevention Research Center, a co-investigator of the study.

The results, presented at the annual American College of Cardiology scientific meeting in New Orleans, add to mounting evidence of the health benefits of dark chocolate.

During the six-week trial, 45 people were given 8 ounces (227 grams) of cocoa without sugar, cocoa with sugar or a placebo each day.

An upper arm artery's ability to relax and expand to accommodate increased blood flow -- known as flow mediated dilation (FMD) -- was measured using high-frequency ultrasound before and after daily cocoa or placebo consumption.

Of the 39 subjects who completed the trial, FMD improved significantly in both cocoa groups -- by 2.4 percent among those who had it without sugar and 1.5 percent among those who had it with sugar. It dropped 0.8 percent in the placebo group.

"While the findings from this study do not suggest that people should start eating more chocolate as part of their daily routine, it does suggest that we pay more attention to how dark chocolate and other flavonoid-rich foods might offer cardiovascular benefits," Njike said.

Swedish researchers believe that they have demonstrated the blood pressure-lowering effect of orally ingested inorganic nitrate similar to that contained in many vegetables, supporting the beneficial cardiovascular effects associated with a diet rich in fruit and vegetables. In a small, short-term study, they showed that short-term dietary supplementation with inorganic nitrate reduced diastolic blood pressure (DBP) in young, normotensive adults. A report of the study, led by Prof. Eddie Weitzberg, MD, PhD (Karolinska Institute, Stockholm), and supported by the Swedish Research Council, the Swedish Heart and Lung Foundation, and the European Commission, has been published in The New England Journal of Medicine.[13] The study was based on the theory that inorganic nitrate is converted by symbiotic bacteria in the oral cavity into nitrite, NO, and secondary reaction products with vasodilating and tissue-protective properties.[14]

Prof. Weitzberg and his colleagues examined the effect of 3-day dietary supplementation with either sodium nitrate 0.1 mmol/kg of body weight per day or sodium chloride 0.1 mmol/kg per day (placebo) on blood pressure in 17 physically active, healthy volunteers (15 men and 2 women; mean age, 24 years; all nonsmokers). Subjects were randomized in a double-blind, crossover fashion for 2 different treatment periods during which the subjects received either nitrate or placebo, separated by a washout period of at least 10 days. During treatment, all subjects avoided foods with a moderate-to-high nitrate content. After nitrate supplementation, DBP and mean arterial pressure were significantly lower compared with placebo by an average of 3.7 mm Hg (P < .002) and 3.2 mm Hg (P < .003), respectively. Plasma nitrate and nitrite levels were significantly higher after nitrate ingestion than after placebo ingestion.

Prof. Weitzberg and his colleagues pointed out that the daily nitrate dose used in their study was equivalent to the amount normally found in 150-250 g of a nitrate-rich vegetable, such as spinach, beetroot, or lettuce. They noted that the Dietary Approaches to Stop Hypertension (DASH) diet, which recommends eating 4-5 servings of vegetables daily, has been shown in clinical trials to reduce blood pressure,[15-18] although no individual nutrient has been identified as responsible for this effect. The researchers noted that the blood pressure effect achieved with nitrate supplementation in their study was similar to that seen in the control group in the DASH study.[15] They do not know the mechanism by which nitrate may lower blood pressure and/or whether the effect can be maintained over the long term. These need to be clarified in future studies, they say, and they plan to do these in Sweden.