Carbohydrates and heart disease

Atherogenic dyslipidemia is a lipoprotein profile that predisposes one to cardiovascular disease. Grundy (1997) characterizes it by four markers: 1) a borderline high-risk LDL cholesterol (130 to 159 mg/dL), 2) moderately raised (often high normal) triglycerides (greater than 150 mg/dL), 3) small LDL particles, and 4) low HDL cholesterol (less than 40 mg/dL for men and 50 mg/dL for women). The third marker is due to data indicating that not all LDL particles are atherogenic; a preponderance of small, dense LDL particles (known as a pattern B phenotype) is associated with increased coronary artery disease (Austin et al., 1988). The presence of atherogenic dyslipidemia itself is a marker for metabolic syndrome.

Source:

Ronald Krauss and colleagues have convincingly shown that changes in carbohydrate intake profoundly affects LDL phenotypes (reviewed in Krauss, 2001). The figure below is a nice summary of the basic observation that restricting carbohydrates reduces the incidence of the atherogenic LDL particle pattern. Note especially the apparent continuity of the effect, and the fact that the carbohydrates are not even severely restricted (certainly nowhere near the levels required to induce ketosis). If you have a half hour to spare, you can catch a recent webcast talk by Krauss summarizing the Pathophysiology of Atherogenic Dyslipidemia.

Source: Krauss, 2001

If you want to full scoop on recent research on the relationship between carbohydrates and dyslipidemia and metabolic syndrome, definitely take the time to check out this review article from Jeff Volek and colleagues (it's technically still in press, but you can grab the galley proofs online). It covers a lot of ground, and is well worth the effort.

Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome.

Volek JS, Fernandez ML, Feinman RD, Phinney SD.

Department of Kinesiology, University of Connecticut

Abstract: Abnormal fatty acid metabolism and dyslipidemia play an intimate role in the pathogenesis of metabolic syndrome and cardiovascular diseases. The availability of glucose and insulin predominate as upstream regulatory elements that operate through a collection of transcription factors to partition lipids toward anabolic pathways. The unraveling of the details of these cellular events has proceeded rapidly, but their physiologic relevance to lifestyle modification has been largely ignored. Here we highlight the role of dietary input, specifically carbohydrate intake, in the mechanism of metabolic regulation germane to metabolic syndrome. The key principle is that carbohydrate, directly or indirectly through the effect of insulin, controls the disposition of excess dietary nutrients. Dietary carbohydrate modulates lipolysis, lipoprotein assembly and processing and affects the relation between dietary intake of saturated fat intake and circulating levels. Several of these processes are the subject of intense investigation at the cellular level. We see the need to integrate these cellular mechanisms with results from low-carbohydrate diet trials that have shown reduced cardiovascular risk through improvement in hepatic, intravascular, and peripheral processing of lipoproteins, alterations in fatty acid composition, and reductions in other cardiovascular risk factors, notably inflammation. From the current state of the literature, however, low-carbohydrate diets are grounded in basic metabolic principles and the data suggest that some form of carbohydrate restriction is a candidate to be the preferred dietary strategy for cardiovascular health beyond weight regulation.

PMID: 18396172

Fasting and your body temperature

Fasting slows down your metabolism in order to reduce energy expenditure (Wang et al., 2004), which may be one of the reasons that animals live longer on dietary regimens such as caloric restriction or intermittent fasting (Liu & Walford, 1972; Rikke & Johnson, 2004; Salerian & Saleri, 2006). Under these regimens metabolic slowing manifests itself in a number of ways, usually a reduction in daily activity and a lower body temperature (Rikke et al., 2003; Severinsen & Munch, 1999). Lane and colleagues (1996) showed that caloric restriction in rhesus monkeys results in a rapid reduction in body temperature, and that the reduction endures for the duration of caloric restriction (in this case years).Humans under caloric restriction also exhibit reductions, albeit smaller, in body temperature. Heilbronn and colleagues (2006) randomized subjects into 1 of 4 groups for 6 months: (1) control (weight maintenance diet); (2) calorie restriction (25% calorie restriction of baseline energy requirements); (3) calorie restriction with exercise (12.5% calorie restriction plus 12.5% increase in energy expenditure by structured exercise); and (4) very low-calorie diet (very low-calorie diet [890 kcal/d] until 15% reduction in body weight, followed by a weight maintenance diet).
Group (3) is particularly interesting, showing that even relatively mild caloric restriction (a degree that can easily occur while intermittently fasting) decreases body temperature. So reducing body temperature is a common response to dietary restrictions, and together with decreases in physical activity are the largest contributors to reducing energy expenditures (reductions in basal metabolism occur, but apparently contribute relatively little).

Evidence suggests that the severity of the dietary restriction dictates the degree of temperature reduction. Rats subjected to total starvation versus caloric restriction (75%, which is quite severe) experienced a significantly greater reduction in body temperature for the duration of restriction, with temperatures in both groups normalizing once ad libitum feeding was reinstated (Severinsen & Munch, 1999).
I haven't found any primate data on body temperature under intermittent fasting, but mice exit torpor, which is a reduction in body temperature during inactive parts of the diurnal cycle, when intermittently fed double and triple rations (Rikke et al., 2003; see also Wan et al., 2003 for body temperature reductions under a more conventional alternate day fasting regimen). Presumably, part of this is due to the caloric expenditure associated with digesting a large meal.

The data also suggest, at least in this mouse strain, that when torpor is re-entered during the fast between meals, that the decrease in body temperature is particularly dramatic.

It's tempting to infer that caloric restriction and/or intermittent fasting cause reductions in body temperature which in turn causes the prolonged lifespans associated with both these dietary regimens. However, a recent experiment using genetically-engineered mice clearly shows that this cannot be the whole story. Conti and colleagues (2006) created transgenic mice where the preoptic area of the hypothalamus, which regulates body temperature, was warmer than normal. This tricked the brain into reducing body temperature by roughly half a degree Celsius, within the range attainable by dietary restrictions or meal patterning. These mice lived 10-20% longer than wild-type mice (in the figure black=wild-type, red=mutant).
The increase in lifespan occurred despite the fact that the transgenic mice ate as much as the normal mice, and actually weighed slightly more. These results indicate that a reduction in body temperature can lengthen lifespan independently of caloric restriction or intermittent fasting. It will be interesting to see whether calorically restricting or intermittently fasting these transgenic mice will lead to even longer lifespans.

I suspect that in practice the wide variation in fasting regimens results in wide variation in the magnitude of body temperature reductions. These factors probably interact with variations in the degree to which individual metabolisms react to dietary restrictions and meal patterning. I would venture to guess based on the evidence that people subjecting themselves to more severe caloric restriction or longer fasts (more severe caloric restriction on a local time scale) will experience the greatest reductions in body temperature. It's unclear to me whether this translates to impaired cold tolerance, although some first-hand reports suggest that it might.

Eating more while gaining less

Seems that exercise is a good overall appetite suppressant. Perhaps not surprising, but it seems that our odd eating habits after a workout are probably producing a balanced (or potentially net negative) energy intake. Makes a good argument for us to get a pull-up bar in the lab--that way we can do a mini-ladder sometime before lunch every day to help ensure our calories are devoted to increasing muscle mass and not 'middle' mass.

Effects of exercise on gut peptides, energy intake and appetite