High Protein Diets and Colonic Health

High-Protein Diets and Colon Cancer Risk

High-Protein Diets Increase the Prevalence of Colon Cancer Risk Factors

The increased prevalence of high protein, low carbohydrate diets is evidence of the need for effective weight loss strategies. These diets help individual's lose weight by producing a feeling of satiety that limits calorie intake. The health benefits associated with this type of diet are associated primarily with weight loss and can include improved insulin sensitivity. What is poorly understood is how these diets might affect health in negative ways over the long-term.

Several recent studies have highlighted the role of intestinal flora in mediating colon cancer risk, in particular the metabolic conversion of digestion-resistant carbohydrates (fiber) to short-chain fatty acids through fermentation. One of these short-chain fatty acids, butyrate, serves as the main energy source for the colonic epithelium and has been shown to have anti-inflammatory (reviewed by Russell et al., 2011), anti-proliferative, anti-apoptotic, and anti-neoplastic properties (reviewed by O'Keefe et al., 2007, p. 180S). The enteric fermentation of fiber by bacteria also produces phenolic compounds that have been shown to have antioxidant and anti-neoplastic properties (reviewed by Russell et al., 2011). Nitrosamine and heterocyclic amine production is increased by a diet rich in red meat, in part due to the increased consumption of heme iron, and these byproducts have been linked to an increased risk of colon cancer (reviewed by O'Keefe et al., 2007; Russell et al., 2011).

What has yet to be studied in detail is the effect of high-protein low-carbohydrate diets on colon health, in particular the effects of such a diet on the intestinal biome. The authors (Russell et al., 2011) therefore analyzed the metabolic patterns produced by this popular weight loss diet.

Methodology

The study subjects were obese adult males (N = 17), with a mean body weight of 111.9 kg (264 pounds) and a range of 86.3-154.8 kg (190-341 pounds). The mean body mass index (BMI) was 35.8 kg/m2, with a range of 30-48.5). The exclusion criteria were a history of gastrointestinal problems, antibiotic use within the last 3 months, and the use of drugs known to influence fecal microbiota.

Three diets were provided, a weight maintenance diet, high-protein moderate-carbohydrate (HPMC) diet, and a high-protein low-carbohydrate (HPLC) diet. The energy density between the three diets was equivalent. The weight maintenance diet was provided for all subjects at the beginning of the study period for 3-5 days. After the initial maintenance period they were put on either the HPMC or HPLC diet for 28 days. This was a randomized, cross-over study so each subject subsisted on each diet for 28 days during the 9-week study period.

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Maintenance Diet (5 days):

85 g protein

116 g fat

360 g carbohydrates

HPMC Diet (28 days):

139 g protein

82 g fat

181 g carbohydrates

HPLC Diet (28 days):

137 g protein

143 g fat

22 g carbohydrate

Fresh-frozen fecal matter was analyzed for bacterial counts (fluorescent in situ hybridization) and the concentration of short-chain fatty acids (gas chromatography) and ammonia (VIS spectrophotometry) were determined. Extracted fecal water was analyzed for N-nitroso compound concentrations by assessing nitric oxide release in a thermal energy analyzer. Phenolics, indoles, bile acids, and heterocyclic amines were separated by HPLC (high performance liquid chromatography) and quantified by mass spectrometry.

Results and Summary

The average weight loss experience by the study subjects was 3.59% and 5.77% of body weight for the HPMC and HPLC diets, respectively, which explains why these diets are so popular. In terms of health though, a 50% or 94% reduction in the amount of carbohydrates consumed resulted in 7% and 32% (p < 0.001) reductions in short-chain fatty acid concentrations, respectively. Of particular concern were the observed 12% and 50% (p < 0.001) reductions in fecal butyrate concentrations for the HPMC and HPLC diets, respectively. The reduction in butyrate concentrations would force epithelial cells to use alternate sources of energy, and lower the anti-inflammatory, anti-proliferative, anti-apoptotic, and anti-neoplastic activities normally present in a carbohydrate-balanced diet.

N-nitroso compound concentrations in fecal matter were increased by 3.6- (p < 0.001) and 5.4-fold (p < 0.001) for the HPMC and HPLC diets, respectively, as was the pH of the fecal-extracted water. These diet-induced changes suggest that high-protein low-carbohydrate diets increase the prevalence of compounds linked to colon cancer. Subjecting fecal extracts to high performance liquid chromatography and mass spectrometry produced a large amount of information. Overall, the most significant findings were a significant decrease in plant-derived indoles and phenolic compounds and their derivatives. Changes in bile acid concentrations showed no clear pattern. The authors interpreted this data as being consistent with high-protein low-carbohydrate diets decreasing the concentrations of cancer-protective metabolites and increasing those posing a hazard.

Overall fecal bacteria counts were lower in both high-protein diets (p < 0.012). Importantly, the prevalence of the butyrate producer Roseburial Eubacterium rectale were significantly (p < 0.001) reduced in subjects on the HPLC diet, which may explain the 50% reduction in fecal butyrate concentrations. The prevalence of the butyrate producer Faecalibacterium prausnitzii was unchanged and could therefore be one of the primary sources of the butyrate detected. The authors suggested that the decline in Roseburial E. rectale counts may have been driven by the increased pH and the reduction in fiber associated with the HPLC diet.

The authors concluded that the more moderate high-protein diet (HPMC) was able to maintain a relatively healthy profile in terms of butyrate concentration and bacterial diversity. This conclusion implies that less severe high-protein diets may help maintain a healthy intestinal environment, while still experiencing significant weight loss. This conclusion though, is undermined by the dramatic increase in N-nitroso compounds and phenyl acetic acids (PAA) detected in the fecal matter from subjects on the moderate high-protein diet. These compounds and their derivatives have been linked to an increased risk of colon cancer (reviewed by O'Keefe et al., 2007; Russell et al., 2011).

Critique