The focus that the medical and scientific establishments put on cholesterol as a risk factor for cardiovascular disease (e.g. heart disease and stroke) can means that other risk factors may not the attention they might deserve. For example, blood fats known as triglycerides have been linked with cardiovascular disease (CVD). Just a couple of weeks ago, a study published in the Journal of the American Medical Association that found that higher levels of triglycerides were associated with an increased risk of ischaemic stroke (stroke caused by a blocking off of blood vessels in the brain rather than bleeding blood vessels) [1]. Last year saw the publication of research in the same journal which linked raised triglyceride levels with an enhanced risk of heart disease, heart attack and death in both men and women [2].
This evidence does not prove that raised triglyceride levels cause CVD, but the association may be important because it is possible that triglycerides do play a causal role here. Even with the state of the evidence as it stands, I think it’s important to keep an eye on triglyceride levels when individuals take steps to reduce their risk of CVD by, say, reducing their cholesterol level.
The standard dietary approach for reducing cholesterol is to eat a low fat diet, specifically a diet low in saturated fat. Such a diet may reduce cholesterol levels, though it should be borne in mind I think that such a dietary strategy has been proven to be ineffective for the purpose of saving lives [3]. But the other thing to bear in mind is that when individuals cut back on fat, they generally fill up on carbs. The importance of this is that carbohydrate is a major driver of triglyceride levels in the bloodstream [4]. What this means is that eating a low-carb diet might temper triglyceride levels and perhaps CVD risk too.
Not so long ago I reported on a review of the impact of carbohydrate-controlled diets in individuals with diabetes [5]. Even though some of the diets assessed in this review were not particularly low in carbohydrate, overall this dietary intervention led to a lowering of triglyceride levels of about a third. Even more recently, I reported on a study which found that a low-carb diet outperformed a low-fat one when it comes to reducing triglyceride levels (as well as weight loss) [6].
Further support for the idea that reducing triglyceride levels by eating less carb (and the other biochemical benefits that may come with this) may reduce the risk of cardiovascular disease might come from studies which find a link between eating less carbohydrate and reduced disease risk. As it happens, we do have some evidence to this effect. Carbohydrates that are generally disruptive to blood sugar (and therefore insulin) levels (high glycaemic index/load carbs) are known to raise triglyceride levels, and they are also associated with an increased risk of CVD [7]. However, as this last study points out and I discuss in the relevant blog post, eating a carb-fuelled diet may induce many changes in the body that would be expected to increase CVD risk. There’s good reason to believe that eating a low-fat, high-carb diet might actually increase the risk of CVD, and we therefore need to be wary about swallowing traditional advice about such diets.
References:
1. Freiberg JJ, et al. Nonfasting Triglycerides and Risk of Ischemic Stroke in the General Population. JAMA 2008;300:2142 – 2152
2. Nordestgaard BG, et al. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007;298(3):299-308
3. Studer M, et al. Effect of different antilipidemic agents and diets on mortality. Archives of Internal Medicine. 2005;165:725-730
4. Parks EJ. Effect of dietary carbohydrate on triglyceride metabolism in humans. J Nutr. 2001;131(10):2772S-2774S.
5. Kirk JK, et al. Restricted-carbohydrate diets in patients with type 2 diabetes: a meta-analysis. Journal of the American Dietetic Association. 2008;108:91-100
6. Shai I, et al. Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet. NEJM 2008;359:229-241
7. Brand-Miller, et al. The Glycemic Index and Cardiovascular Disease Risk. Current Atherosclerosis Reports 2007;9:479-485
Because all the orthodox advice pushes the low-fat diet, it is not generally recognised that the main driver of fat deposition is insulin. Fat cannot get into storage in adipose unless there is insulin in the bloodstream. When is insulin at its highest in the bloodstream? When we have eaten a meal containing high-GI CARBOHYDRATE. As for cholesterol, a low-fat diet does very little to reduce LDL levels because A) cholesterol is not a fat and is not made from fat and B) more than 80% of cholesterol is made by our own liver anyway. Again insulin is the prime mover. The liver makes cholesterol ONLY when insulin is high in the bloodstream. When is insulin at its highest in the bloodstream? When we have eaten a meal containing high-GI CARBOHYDRATE ….
Janet : Do you have any refs for what you say about the liver?
Hilda, I guess it’s standard physiology. Firstly, the immediate precursor for cholesterol is acetyl CoA, which is in its turn synthesised not only during fatty acid metabolism but from pyruvate during carbohydrate metabolism, after glycolysis and before the Krebs cycle. (In other words, the precursor to cholesterol is just as much a product of carbohydrate metabolism – and protein, to a lesser extent – as it is of fatty acid metabolism). Secondly, cholesterol can only be made when the enzyme HMGCoA reductase is present, and this enzyme is only synthesised when glucose (and therefore insulin) are at high circulating levels. Therefore it is logical to conclude that people with high circulating glucose have the highest synthesis of cholesterol, subject to a number of metabolic checks and balances. (We don’t hear about this, I believe, because everyone is so hung up on how bad FAT is for us, that the influence of carbohydrate is ignored.) There’s a reference to increased cholesterol synthesis after administration of insulin: Feillet, C et al (October 1994). Evidence for a short-term stimulatory effect of insulin on cholesterol synthesis in newly insulin-treated diabetic patients. Metabolism. 43 (10): 1233-40. And another to high cholesterol levels in people with insulin resistance: Pihlajamäki, J et al (March 2004). Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men. Journal of Lipid Research. 45: 507-512. That’s before we get to one of the major reasons why our liver synthesises cholesterol in the first place – in response to an inflammatory process going on in the endothelium, the lining of blood vessels – cholesterol migrates to the endothelium in order to plug any gaps that might be being caused by the inflammatory process. (And when is inflammation rife in endothelium? When we eat a diet high in sugars). It seems that the small effect of statin drugs on the incidence of heart disease is more to do with their inhibitory effect on inflammation than of a reduction in the synthesis of cholesterol.
Thanks Janet. Great explanation!