Long-Term Low-Protein Diet Reduces Markers of Cancer Risk

ST. LOUIS, Dec. 7 -- Long-term lifestyle modifications, particularly cutting way back on the consumption of protein, seems to be associated with reduced levels of markers of cancer risk, according to a small observational study.

Plasma growth factors and hormones, which the authors identified as associated with cancer risks, were significantly improved among runners and those on a protein- and calorie-restricted diet, compared with sedentary individuals on a normal Western diet, found Luigi Fontana, M.D., Ph.D., of Washington University here, and colleagues.

The investigators evaluated 21 persons who had been on a raw food or vegetarian diet for at least two years (mean 4.4 years); 21 men and women who participated in endurance running (average 48 miles per week, average 21 years); and 21 healthy, nonobese control subjects on typical Western diets.

Endurance runners were matched with the low-protein, low-calorie diet group by age, sex, and BMI. The healthy, nonobese controls, eating a typical Western diet. had higher BMIs than the low calorie group or the endurance runners ((26.5 2.7_vs. 21.3 3.1 and 21.6 1.6 respectively, P?0.003 and P?0.002 versus controls, respectively).

They were matched with the low-protein, low-calorie diet group by age, sex, and height the investigators reported in the December issue of the American Journal of Clinical Nutrition.

Protein intake averaged 0.73 g/kg of body weight daily for the diet group. Both runners and controls ate about twice as much protein (1.6 g and 1.23 g/kg of body weight daily, respectively). The recommended daily protein intake is 0.8 grams.

A lower protein diet appeared to offer an advantage in cancer-risk marker reduction over endurance running, the researchers said. They found that plasma concentrations of insulin and insulin-like growth factor (IGF, which promotes cell proliferation, inhibits cell death and increases risk of breast, prostate and colon cancers) were lower in dieters and runners compared with controls. They reported, respectively:

• Insulin concentrations of 2.8 and 2.1 versus 5.9 ?U/mL (P=0.0001 for both),
• Plasma IGF- I levels of 139 and 177 versus 201 ng/mL (P?0.008 for diet versus both), and
• IGF-I to IGF binding protein 3 ratios of 0.033 and 0.044 versus 0.046 (P?0.008 for diet versus both).

"Low protein intake may have additional protective effects because it is associated with a decrease in circulating IGF-I independent of body fat mass," they wrote.

Another marker of cancer risk is sex hormone levels. Previous research has linked higher plasma concentrations of these hormones, such as estradiol and testosterone, and low plasma sex hormone binding globulin concentrations with an increased risk of breast and endometrial cancers.

In the study, free sex hormones were lowest and sex hormone-binding globulin highest for the calorie- and protein-restricted diet group. Compared to runners and controls, the findings were:

• Free androgen index of 7.8, 9.8 and 12.6, respectively, for men and 0.6, 1.1 and 1.5 for women (P?0.05 for male dieters versus controls), and
• Sex hormone binding globulin levels of 257, 205, and 164 nmol/L for men and 440, 323, and 176 nmol/L for women (P?0.05 for male and female dieters versus controls).

Leptin levels were significantly lower for both lifestyle modification groups compared to controls. The researchers found:

• For men, levels were 2.0 ng/mL for dieters, 1.8 ng/mL for runners, and 5.3 ng/mL for controls (P?0.027 and P?0.008 versus control, respectively), and
• For women, levels were 6.3 ng/mL for dieters, 5.2 ng/mL for runners, and 27.2 ng/mL for controls (P?0.027 and P?0.008 versus control, respectively).

High sensitivity C-reactive protein levels were also significantly lower for the dieters and runners compared to controls (0.52 and 0.75 versus 2.61 mg/L, (P?0.027 and P=0.05 versus control, respectively).

"Data from epidemiologic studies indicate that obesity is a risk factor for several types of cancer, including colon, breast, endometrial, kidney, and pancreas cancer," Dr. Fontana and colleagues wrote. "Increased adipose tissue may be involved in the pathogenesis of specific cancers, because of adipokine production, insulin resistance, hyperinsulinemia, and chronic inflammation."

The study participants included only those without evidence of chronic disease, such as cardiovascular, lung, gastrointestinal, or autoimmune diseases or type 2 diabetes or cancer. None smoked or was taking hormone replacement therapy.

All of those in the diet and control groups were sedentary with less than one hour of regular endurance exercise each week. Both the control and running groups ate typical diets with meat.

The researchers said their findings "help to identify potential mechanisms by which long-term lifestyle modifications in diet or physical activity can selectively reduce circulating factors that are associated with increased cancer risk."

But they cautioned that the study could not show causal relations and did not evaluate the prevalence of cancer itself. It is not known whether these surrogate markers will reflect the incidence of cancer in the study participants, they pointed out. They also wrote that "the small sample size and the cross-sectional nature of this study do not allow us to exclude that other unknown factors could play a role in the reported differences."

Further studies with larger sample sizes will be needed to confirm the findings.

They warned that a low-protein diet may not be right for everyone, particularly since it may reduce bone mass and strength in older individuals with already low serum IGF-I concentrations.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Research Resources of the National Institutes of Health. The authors declared no conflicts of interest.