This is a very interesting study. It claims that more cholesterol equates to more muscle hypertrophy, not protein or calories.
[quote=
http://biomedgerontology.oxfordjournals ... /1164.long]It is well accepted that proper nutrition, especially adequate protein, is important to maximize lean mass gains with RET (5,6,13,15,16). When protein consumption was standardized, we observed a strong direct association of dietary cholesterol to the magnitude of lean mass gains that was consistent with the association of serum cholesterol to lean mass gains. This finding was supported by a significant association of dietary cholesterol and change in strength. Moreover, statin users also had greater lean mass gains, independent of dietary and serum cholesterol. This intervention was also associated with significant reductions in systolic and diastolic blood pressure that were not influenced by dietary cholesterol levels.
The results of this study were unexpected given the well-established effects of cholesterol on health and effects of statins on skeletal muscle. It is important to note that a vast majority of these studies do not account for the interaction of these factors with exercise. Nonetheless, we sought alternate explanations for these associations. For example, a sedentary population may have the greatest potential for muscle mass gains, may be more obese, and may consume more cholesterol. However, this is not likely to have affected our results because we selected a population with low physical activity, and obesity was not associated with either dietary cholesterol consumption or muscle gain. The association of cholesterol with other foods, particularly protein, may have also confounded our results. However, we extensively examined protein and found no association with muscle responses. We speculated that this result was due to postexercise protein supplementation (18). It is still possible that a micronutrient such as creatine (not analyzed by our software and known to enhance muscle responses) caused greater muscle mass gains and is also associated to dietary cholesterol (e.g., meat sources). This would not explain the association of blood cholesterol to muscle gain. The well-known limitations of dietary records and their tendency to underestimate intake may be attenuated by the collection of 36 records in 12 weeks. Similar studies typically collect three records at the beginning and at the end of training. This tendency to underestimate dietary intake may be more common in obese individuals; therefore, our failure to identify an association of obesity with muscle gain may have been affected by reporting differences. Even though these results were unexpected, there exists supporting evidence in the literature that cholesterol and statins affect muscle response to RET.
Cholesterol is an essential component of biological membranes. It increases membrane viscosity, which increases the exposure of membrane proteins to extracellular fluids (19). Cholesterol is also essential to the formation of lipid rafts, which function as platforms for the assembly of components of signaling pathways through protein sorting and construction of signaling complexes (20). Cholesterol depletion can induce protein missorting and reduced signal transduction (21,22). Lipid rafts have been implicated as essential for signaling through nitric oxide synthase, protein kinase C-alpha (PKC-?), G-protein ? subunits, insulin receptor, insulin-like growth factor-1 (IGF-1) receptor, tumor necrosis factor-alpha (TNF-?), nuclear factor-kappa B (NF-?B), phosphoinositide kinase-3 (PI3K), protein kinase C (PKC), epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), interleukin-6 (IL-6), extracellular signal-regulated kinase 2 (ERK2), AKT1, and steroid hormone receptor (21–24). These signaling pathways have been identified as contributors to skeletal muscle adaptation to exercise training (23,24). Thus, one possible explanation for greater skeletal muscle hypertrophy in persons with higher dietary and serum cholesterol is improved cellular signaling as a result of greater membrane cholesterol and signaling assembly through lipid rafts.
Cholesterol may also play a role as an essential building block to repair microtears that occur in the skeletal muscle membrane with RET. However, a readily available supply of circulating cholesterol suggests that this may not be the major mechanism of cholesterol-induced muscle hypertrophy. Immediate reductions in serum cholesterol (within 2 hours, lasting up to 72 hours) following exercise causing muscle injury have been suggested to be part of the process to repair the membrane damage (25,26). These microtears are also associated with an acute immune/inflammatory response that is widely believed to play an important role in skeletal muscle hypertrophy through local production of cytokines and anabolic factors to repair damaged tissue (27).
We observed greater hypertrophy in participants using certain statins. This result was unexpected considering that several studies have reported adverse effects of statins on skeletal muscle (9,27). However, statins increase the susceptibility of skeletal muscle to membrane injury in response to an acute exercise challenge (28), which may potentiate hypertrophy if the magnitude of this injury and inflammatory response is directly related to the magnitude of hypertrophy through inflammation-related growth factors. Conversely, a decrease in the synthesis of cholesterol intermediates by statins results in a suppression of isoprenoid derivatives essential for prenylation of Ras and Rho GTPases (29). Reduced function of these GTPases has been shown to decrease myocyte proliferation in cell culture, as they are essential for skeletal muscle differentiation and regulate MyoD and myogenin expression (29). The conflicting observations may be explained by differences in in vivo and in vitro experimental protocols and unique complexity of an exercise intervention.
Recently, it has been proposed that statin-induced reduction in the cholesterol synthesis metabolite isopentenyl-pyrophosphate may explain statin myopathy (30). Isopentenylation of selenocysteine-transfer RNA (sec-tRNA) is required for its role in the expression of selenoproteins (31). Selenoprotein N has been linked to myogenesis and myoregeneration, and a genetic mutation in the Selenoprotein N1 (SEPN1) gene results in several forms of congenital juvenile myopathy with similar features to statin-induced myopathy (32). It is interesting that transgenic mice have been developed that reduces selenoproteins through the expression of a dominant mutant form of sec-tRNA. In response to synergistic ablation, a model of exercise overload, these transgenic mice increased muscle mass ?50% more than their wild-type controls (33). Prior to the synergistic ablation, the AKT and p70s6k phosphorylation states were altered and the increased hypertrophy was blocked by the AKT/mammalian target of rapamycin (mTOR) inhibitor rapamycin. Thus statin inhibition of isopentenyl-pyrophosphate and selenoproteins may explain our observed promotion of hypertrophy with statin use.
The direct association between dietary cholesterol and changes in strength further supports the potential anabolic role of cholesterol. Moreover, the significant indirect association of HDL cholesterol with absolute strength both before and after training highlights the potential role of subfractions in the physiology of this response. Whereas the LDL subfraction delivers cholesterol to tissues and is strongly associated with muscle gain, the HDL subfraction delivers cholesterol away from tissues to be metabolized. Previous studies on cholesterol and muscle characteristics are quite limited; however, Kohl and colleagues (34) reported a strong inverse association, consistent with our findings, between HDL and 1 RM strength for chest and leg press (same as in the present report) in 5460 men.
The results of this study suggest that dietary and serum cholesterol contribute to the skeletal muscle response to resistance exercise, conflicting with recommendations to prevent CVD. The evidence that higher serum cholesterol is associated with greater risk for CVD is clear. However, when confounders of dietary assessment were considered, Kritchevsky and Kritchevsky (35) reported that 1 egg per day (210 mg of cholesterol) was not associated with an elevated risk of coronary events whereas only a small 6% increase in risk was associated with a 200 mg/1000 kcal/d difference. The present study demonstrated a significant reduction in systolic and diastolic blood pressure, and there was not a worsening of serum lipid profile with higher dietary cholesterol. However, the trend toward higher hsCRP suggests at least one cardiovascular risk may be elevated.
Sarcopenia is a prevalent and growing economic burden due to its association with chronic disability and mortality. Exercise interventions are efficacious for prevention and treatment of sarcopenia, although recommendations need to be consistent with other diseases associated with age. The current results clearly suggest and are the first to our knowledge to show that higher dietary and serum cholesterol and statin use are independently associated with greater lean mass responses to RET in this group of generally healthy 60- to 69-year-old men and women. Because cholesterol is negatively associated with cardiovascular health, rigorous efforts to confirm these findings are necessary. Even if results are confirmed, it is necessary to examine changes in cardiovascular risk due to dietary cholesterol consumption (within the context of exercise training) so that reduction in sarcopenia and disability is not at the price of elevated CVD. [/quote]
