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I agree with many of Ravnskov’s present and past points, especially
regarding cholesterol, saturated fat, and statin drugs. Statin drugs lower
C-reactive protein and may confer an anti-inflammatory benefit prior to
the lowering of total and LDL cholesterol.1, 2 Like Dr. Ravnskov, I have
concerns about their risks.3 It also appears that C-reactive protein is a
better marker than lipid profiles suggesting a critical, diffuse
inflammatory process in diabetes and CHD.4, 5 Could it be that saturated
fat, LDL, and other lipids are fairly benign unless they are in a pro-
oxidant environment, and maybe it is the anti-inflammatory effects of the
statins that are most beneficial? Perhaps it is the excess calories that
are often consumed along with saturated fat (rather than the saturated fat
per se) that generate free radical production and exacerbate endothelial
dysfunction.6, 7 Saturated fat consumption has been associated with a rise
in HDL8 and a lowering of Lp(a).9 Identifying the background diet is often
lacking in studies. For example, fiber, which may be low in a high
saturated fat diet, has been shown to be a better predictor of insulin
levels, weight gain, and other risk factors for CHD than total or
saturated fat consumption.10 Metabolic syndrome (along with heart
disease and diabetes) is increasing at an alarming rate.11
Since our genes
haven’t changed in thousands of years, isn’t it likely that changes in our
environment and lifestyles, i.e., exposures, food quality, diet, and
exercise patterns, are contributing to our modern epidemics?
Lifestyle factors have now been established as keys in preventing and
reversing type 2 diabetes12, 13 and CHD,14-16 and evidence supports
lowering glycemic load, eliminating trans fats, and emphasizing
monounsaturated and omega 3 fatty acids. These dietary measures have been
shown to improve glycemic control,17, 18 insulin sensitivity, 19 20 and
lipid profiles,17, 18 21 thereby reducing the risk of diabetes19, 22-24
and coronary heart disease.17, 18, 20, 25, 26 Eating smaller, more
frequent meals spreads out the “nutrient load,” slows absorption of
carbohydrates, helps stabilize insulin and glucose levels,27 may prevent
overproduction of free radicals,6, 7, 28 and can lower total and LDL
cholesterol which may or may not indicate a lower CHD risk.29-31 There
are few long-term studies documenting any diet’s benefits but it would
seem that one cannot dismiss a potential role for certain nutritional
concepts in disease.32 Exercise and level of fitness may also dictate
responses to diet.33, 34 I do agree we need more rational thinking backed
by rigorous and unbiased research.
1. Kendrick M. Finally, proof that statins don't work by lowering
LDL. BMJ 2001; 323:1145 (electronic response to Kmietowicz, Z. BMJ.com).
2. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects
of pravastatin on plasma concentration of C-reactive protein. The
Cholesterol and Recurrent Events (CARE) Investigators [see comments].
Circulation 1999; 100:230-5.
3. Newman T, Hulley S. Carcinogenicity of lipid-lowering drugs. JAMA 1996;
275:55-60.
4. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and
other markers of inflammation in the prediction of cardiovascular disease
in women. N Engl J Med 2000; 342:836-43.
5. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive
protein, interleukin 6, and risk of developing type 2 diabetes mellitus.
Jama 2001; 286:327-34.
6. Dandona P, Mohanty P, Ghanim H, et al. The suppressive effect of
dietary restriction and weight loss in the obese on the generation of
reactive oxygen species by leukocytes, lipid peroxidation, and protein
carbonylation. J Clin Endocrinol Metab 2001; 86:355-62.
7. Plotnick GD, Corretti MC, Vogel RA. Effect of antioxidant vitamins on
the transient impairment of endothelium-dependent brachial artery
vasoactivity following a single high-fat meal. Jama 1997; 278:1682-6.
8. Nicolosi RJ, Wilson TA, Lawton C, Handelman GJ. Dietary effects on
cardiovascular disease risk factors: beyond saturated fatty acids and
cholesterol. J Am Coll Nutr 2001; 20:421S-427S; discussion 440S-442S.
9. Ginsberg J, Kris-Etherton P, Dennis B, et al. Effects of reducing
dietary saturated fatty acids on plasma lipids and lipoproteins in healthy
subjects: The Delta Study, Protocol 1. Arterioscler Trhomb Vasc Biol
1998; 18:441-449.
10. Ludwig DS, Pereira MA, Kroenke CH, et al. Dietary fiber, weight gain,
and cardiovascular disease risk factors in young adults. Jama 1999;
282:1539-46.
11. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome
among US adults - Findings from the Third National Health and Nutrition
Examination Survey. Jama-Journal of the American Medical Association 2002;
287:356-359.
12. Hu FB, Manson JE, Stampfer MJ, et al. Diet, lifestyle, and the risk of
type 2 diabetes mellitus in women. N Engl J Med 2001; 345:790-7.
13. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2
diabetes mellitus by changes in lifestyle among subjects with impaired
glucose tolerance. N Engl J Med 2001; 344:1343-50.
14. Fung TT, Willett WC, Stampfer MJ, Manson JE, Hu FB. Dietary patterns
and the risk of coronary heart disease in women. Arch Intern Med 2001;
161:1857-62.
15. Brown AA, Hu FB. Dietary modulation of endothelial function:
implications for cardiovascular disease. Am J Clin Nutr 2001; 73:673-86.
16. Hu FB, Stampfer MJ, Manson JE, et al. Trends in the incidence of
coronary heart disease and changes in diet and lifestyle in women [see
comments]. N Engl J Med 2000; 343:530-7.
17. Garg A. High monounsaturated-fat diets for patients with diabetes
mellitus: a meta-analysis. Am J Clin Nutr 1998; 67(suppl):577S-82S.
18. Jarvi A, Karlstrom B, Granfeldt Y, Bjorck I, Asp N-G, Vessby B.
Improved glycemic control and lipid profile and normalized fibrinolytic
activity on a low-glycemic index diet in Type 2 diabetic patients.
Diabetes Care 1999; 22:10-18.
19. Hu FB. The role of n-3 polyunsaturated fatty acids in the prevention
and treatment of cardiovascular disease. Drugs of Today 2001; 37:49-56.
20. Vessby B, Unsitupa M, Hermansen K, et al. Substituting dietary
saturated for monounsaturated fat impairs insulin sensitivity in healthy
men and women: The KANWU Study. Diabetologia 2001; 44:312-9.
21. Ford ES, Liu S. Glycemic index and serum high-density lipoprotein
cholesterol concentration among us adults. Arch Intern Med 2001; 161:572-
6.
22. Salmeron J, Ascherio A, Rimm EB, et al. Dietary fiber, glycemic load,
and risk of NIDDM in men. Diabetes Care 1997; 20:545-50.
23. Salmeron J, Hu FB, Manson JE, et al. Dietary fat intake and risk of
type 2 diabetes in women. Am J Clin Nutr 2001; 73:1019-26.
24. Salmeron J, Manson JE, Stampfer MJ, Colditz GA, Wing AL, Willett WC.
Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes
mellitus in women. JAMA 1997; 277:472-7.
25. Liu S, Willett WC, Stampfer MJ, et al. A prospective study of dietary
glycemic load, carbohydrate intake, and risk of coronary heart disease in
US women. Am J Clin Nutr 2000; 71:1455-61.
26. Harper CR, Jacobson TA. The fats of life: the role of omega-3 fatty
acids in the prevention of coronary heart disease. Arch Intern Med 2001;
161:2185-92.
28. Schinkovitz A, Dittrich P, Wascher TC. Effects of a high-fat meal on
resistance vessel reactivity and on indicators of oxidative stress in
healthy volunteers. Clin Physiol 2001; 21:404-10.
29. Edelstein SL, Barrett-Connor EL, Wingard DL, Cohn BA. Increased meal
frequency associated with decreased cholesterol concentrations; Rancho
Bernardo, CA, 1984-1987. Am J Clin Nutr 1992; 55:664-9.
30. Fabry P, Fodor J, Hejl Z, Geizerova H, Balcarova O. Meal frequency and
ischaemic heart-disease. Lancet 1968; 2:190-1.
31. Titan SMO, Bingham S, Welch A, et al. Frequency of eating and
concentrations of serum cholesterol in the Norfolk population of the
European prospective investigation into cancer (EPIC-Norfolk): cross
sectional study. BMJ 2001; 323:1286-.
32. Walker WA. Advances in nutrition education for medical students:
overview. Am J Clin Nutr 2000; 72:865S-867S.
33. Stefanick ML. Physical activity for preventing and treating obesity-
related dyslipoproteinemias. Med Sci Sports Exerc 1999; 31:S609-18.
34. Wei M, Gibbons LW, Kampert JB, Nichaman MZ, Blair SN. Low
cardiorespiratory fitness and physical inactivity as predictors of
mortality in men with type 2 diabetes [see comments]. Ann Intern Med 2000;
132:605-11.
Another perspective on diet and disease
I agree with many of Ravnskov’s present and past points, especially
regarding cholesterol, saturated fat, and statin drugs. Statin drugs lower
C-reactive protein and may confer an anti-inflammatory benefit prior to
the lowering of total and LDL cholesterol.1, 2 Like Dr. Ravnskov, I have
concerns about their risks.3 It also appears that C-reactive protein is a
better marker than lipid profiles suggesting a critical, diffuse
inflammatory process in diabetes and CHD.4, 5 Could it be that saturated
fat, LDL, and other lipids are fairly benign unless they are in a pro-
oxidant environment, and maybe it is the anti-inflammatory effects of the
statins that are most beneficial? Perhaps it is the excess calories that
are often consumed along with saturated fat (rather than the saturated fat
per se) that generate free radical production and exacerbate endothelial
dysfunction.6, 7 Saturated fat consumption has been associated with a rise
in HDL8 and a lowering of Lp(a).9 Identifying the background diet is often
lacking in studies. For example, fiber, which may be low in a high
saturated fat diet, has been shown to be a better predictor of insulin
levels, weight gain, and other risk factors for CHD than total or
saturated fat consumption.10 Metabolic syndrome (along with heart
disease and diabetes) is increasing at an alarming rate.11
Since our genes
haven’t changed in thousands of years, isn’t it likely that changes in our
environment and lifestyles, i.e., exposures, food quality, diet, and
exercise patterns, are contributing to our modern epidemics?
Lifestyle factors have now been established as keys in preventing and
reversing type 2 diabetes12, 13 and CHD,14-16 and evidence supports
lowering glycemic load, eliminating trans fats, and emphasizing
monounsaturated and omega 3 fatty acids. These dietary measures have been
shown to improve glycemic control,17, 18 insulin sensitivity, 19 20 and
lipid profiles,17, 18 21 thereby reducing the risk of diabetes19, 22-24
and coronary heart disease.17, 18, 20, 25, 26 Eating smaller, more
frequent meals spreads out the “nutrient load,” slows absorption of
carbohydrates, helps stabilize insulin and glucose levels,27 may prevent
overproduction of free radicals,6, 7, 28 and can lower total and LDL
cholesterol which may or may not indicate a lower CHD risk.29-31 There
are few long-term studies documenting any diet’s benefits but it would
seem that one cannot dismiss a potential role for certain nutritional
concepts in disease.32 Exercise and level of fitness may also dictate
responses to diet.33, 34 I do agree we need more rational thinking backed
by rigorous and unbiased research.
1. Kendrick M. Finally, proof that statins don't work by lowering
LDL. BMJ 2001; 323:1145 (electronic response to Kmietowicz, Z. BMJ.com).
2. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects
of pravastatin on plasma concentration of C-reactive protein. The
Cholesterol and Recurrent Events (CARE) Investigators [see comments].
Circulation 1999; 100:230-5.
3. Newman T, Hulley S. Carcinogenicity of lipid-lowering drugs. JAMA 1996;
275:55-60.
4. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and
other markers of inflammation in the prediction of cardiovascular disease
in women. N Engl J Med 2000; 342:836-43.
5. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive
protein, interleukin 6, and risk of developing type 2 diabetes mellitus.
Jama 2001; 286:327-34.
6. Dandona P, Mohanty P, Ghanim H, et al. The suppressive effect of
dietary restriction and weight loss in the obese on the generation of
reactive oxygen species by leukocytes, lipid peroxidation, and protein
carbonylation. J Clin Endocrinol Metab 2001; 86:355-62.
7. Plotnick GD, Corretti MC, Vogel RA. Effect of antioxidant vitamins on
the transient impairment of endothelium-dependent brachial artery
vasoactivity following a single high-fat meal. Jama 1997; 278:1682-6.
8. Nicolosi RJ, Wilson TA, Lawton C, Handelman GJ. Dietary effects on
cardiovascular disease risk factors: beyond saturated fatty acids and
cholesterol. J Am Coll Nutr 2001; 20:421S-427S; discussion 440S-442S.
9. Ginsberg J, Kris-Etherton P, Dennis B, et al. Effects of reducing
dietary saturated fatty acids on plasma lipids and lipoproteins in healthy
subjects: The Delta Study, Protocol 1. Arterioscler Trhomb Vasc Biol
1998; 18:441-449.
10. Ludwig DS, Pereira MA, Kroenke CH, et al. Dietary fiber, weight gain,
and cardiovascular disease risk factors in young adults. Jama 1999;
282:1539-46.
11. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome
among US adults - Findings from the Third National Health and Nutrition
Examination Survey. Jama-Journal of the American Medical Association 2002;
287:356-359.
12. Hu FB, Manson JE, Stampfer MJ, et al. Diet, lifestyle, and the risk of
type 2 diabetes mellitus in women. N Engl J Med 2001; 345:790-7.
13. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2
diabetes mellitus by changes in lifestyle among subjects with impaired
glucose tolerance. N Engl J Med 2001; 344:1343-50.
14. Fung TT, Willett WC, Stampfer MJ, Manson JE, Hu FB. Dietary patterns
and the risk of coronary heart disease in women. Arch Intern Med 2001;
161:1857-62.
15. Brown AA, Hu FB. Dietary modulation of endothelial function:
implications for cardiovascular disease. Am J Clin Nutr 2001; 73:673-86.
16. Hu FB, Stampfer MJ, Manson JE, et al. Trends in the incidence of
coronary heart disease and changes in diet and lifestyle in women [see
comments]. N Engl J Med 2000; 343:530-7.
17. Garg A. High monounsaturated-fat diets for patients with diabetes
mellitus: a meta-analysis. Am J Clin Nutr 1998; 67(suppl):577S-82S.
18. Jarvi A, Karlstrom B, Granfeldt Y, Bjorck I, Asp N-G, Vessby B.
Improved glycemic control and lipid profile and normalized fibrinolytic
activity on a low-glycemic index diet in Type 2 diabetic patients.
Diabetes Care 1999; 22:10-18.
19. Hu FB. The role of n-3 polyunsaturated fatty acids in the prevention
and treatment of cardiovascular disease. Drugs of Today 2001; 37:49-56.
20. Vessby B, Unsitupa M, Hermansen K, et al. Substituting dietary
saturated for monounsaturated fat impairs insulin sensitivity in healthy
men and women: The KANWU Study. Diabetologia 2001; 44:312-9.
21. Ford ES, Liu S. Glycemic index and serum high-density lipoprotein
cholesterol concentration among us adults. Arch Intern Med 2001; 161:572-
6.
22. Salmeron J, Ascherio A, Rimm EB, et al. Dietary fiber, glycemic load,
and risk of NIDDM in men. Diabetes Care 1997; 20:545-50.
23. Salmeron J, Hu FB, Manson JE, et al. Dietary fat intake and risk of
type 2 diabetes in women. Am J Clin Nutr 2001; 73:1019-26.
24. Salmeron J, Manson JE, Stampfer MJ, Colditz GA, Wing AL, Willett WC.
Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes
mellitus in women. JAMA 1997; 277:472-7.
25. Liu S, Willett WC, Stampfer MJ, et al. A prospective study of dietary
glycemic load, carbohydrate intake, and risk of coronary heart disease in
US women. Am J Clin Nutr 2000; 71:1455-61.
26. Harper CR, Jacobson TA. The fats of life: the role of omega-3 fatty
acids in the prevention of coronary heart disease. Arch Intern Med 2001;
161:2185-92.
27. Jenkins DJ. Carbohydrate tolerance and food frequency. Br J Nutr 1997;
77 Suppl 1:S71-81.
28. Schinkovitz A, Dittrich P, Wascher TC. Effects of a high-fat meal on
resistance vessel reactivity and on indicators of oxidative stress in
healthy volunteers. Clin Physiol 2001; 21:404-10.
29. Edelstein SL, Barrett-Connor EL, Wingard DL, Cohn BA. Increased meal
frequency associated with decreased cholesterol concentrations; Rancho
Bernardo, CA, 1984-1987. Am J Clin Nutr 1992; 55:664-9.
30. Fabry P, Fodor J, Hejl Z, Geizerova H, Balcarova O. Meal frequency and
ischaemic heart-disease. Lancet 1968; 2:190-1.
31. Titan SMO, Bingham S, Welch A, et al. Frequency of eating and
concentrations of serum cholesterol in the Norfolk population of the
European prospective investigation into cancer (EPIC-Norfolk): cross
sectional study. BMJ 2001; 323:1286-.
32. Walker WA. Advances in nutrition education for medical students:
overview. Am J Clin Nutr 2000; 72:865S-867S.
33. Stefanick ML. Physical activity for preventing and treating obesity-
related dyslipoproteinemias. Med Sci Sports Exerc 1999; 31:S609-18.
34. Wei M, Gibbons LW, Kampert JB, Nichaman MZ, Blair SN. Low
cardiorespiratory fitness and physical inactivity as predictors of
mortality in men with type 2 diabetes [see comments]. Ann Intern Med 2000;
132:605-11.
Competing interests: No competing interests