B A Ochia
Coronary heart disease (CHD) is undoubtedly increasing at an alarming rate throughout the developed world where it is now regarded as a number one killer. Even in developing countries the incidence of CHD is rising as people’s lifestyles and eating habits are being ‘westernised’.
Serum cholesterol value has been incriminated, from various epidemiological and animal experiments, as one of the major risk factors for CHD. Evidence exists that early atherosclerotic plaque is made up of foam cell macrophages loaded with cholesterol, which is derived from the cellular uptake of oxidatively modified low-density lipoprotein6. It is no wonder then that in many western countries there have been recommendations to lower serum cholesterol content.
What is generally not well known, however, is the fact that either a reduction in serum total cholesterol (TC) or a persistently low cholesterol concentration may be associated with serious consequences, including increased mortality from suicide, haemorrhagic stroke, cancer, trauma and various disorders not related to cancer or CHD1, 2, 3, 4, 5. The reasons for the association remain unclear, although several studies have been made to find possible explanations. Freedman et al1 showed that serum TC level can influence various behaviours. Persons with low TC levels have early or occult disease that eventually leads to death5, or have endothelial injury resulting from risk factors such as hypertension, smoking or diabetes6. A group of Japanese researchers led by Konishi3 advanced a plausible argument that low TC concentration plays a causal role in haemorrhagic stroke by proposing that low TC fosters degenerative changes in intra-cerebral arteries through increased fragility of the media muscle cells. Low TC can change the concentration of cholesterol in cell membrane, thereby modifying its permeability to toxins and influencing its composition. Some of these studies are summarised below.
Freedman et al1 examined the cross-sectional relation of several psychological characteristics to levels of TC, high-density lipoprotein (HDL) cholesterol and triacylglycerol among 3490 US male army veterans 31 to 45 years old. Of the men 697 had cholesterol values 5 mg/100 ml higher than normal. This group was diagnosed with general anxiety disorder due probably to increased blood catecholamine concentration. Another 325 of the men, with blood cholesterol values 7 mg/100 ml lower had normal, were significantly associated with antisocial personality disorder. Neither HDL cholesterol nor triacyglycerol was associated with any diagnosis. The authors cautioned that, since the recommendations to lower serum cholesterol values apply to a large proportion of adults, further research is needed to clarify the possible associations between cholesterol values and behaviour; and if a subset of persons is considered particularly sensitive to behavioural effects of cholesterol lowering, the benefits and risks may need to be considered further. Furthermore, they called for caution, particularly in the chronic use of drugs in asymptomatic persons, and for careful monitoring of mental health and non-CHD morbidity and mortality in clinical trials.
In their epidemiological study Manolio et al5 tested the possibility that persons with low TC values have early or covert disease. The subjects who participated in the Cardiovascular Health Study comprised 2091 men and 274 women 65 to 100 years old. Cholesterol values of 160 mg/100 ml, or less, were found in 11.6% of men and 3.7% of women, and increased in prevalence with age. After adjustment for age, the low TC values were associated with a two-fold increased prevalence of treated diabetes in men and women and with a two-fold increased prevalence of cancer diagnosed in the preceding 5 years in women only. Low cholesterol value was also associated with lower levels of haemoglobin, albumin and factor VII, suggesting a link with hepatic synthetic function. It was possible that two distinct sub-groups were present in the low-TC group, making detection and interpretation of the associations very difficult.
The results of cohort studies and of randomised trials of cholesterol-lowering interventions by Muldoon et al2 showed that increased suicide and traumatic death rate were associated with low TC.
Jacobs and Blackburn4 reviewed some of those studies and wondered whether the observed low TC-disease associations were indeed real or manifestation of other confounding factors. They considered several models and derived a number of conclusions. Some models predicted that the declines in total mortality rate were consistent with declines actually observed in the US studies, as population means of TC and other cardiovascular risk factors had declined. Some implied that little harm is done to those having low TC based on the current, population-wide TC-lowering strategies, because already low TC levels are relatively little changed by such population strategies. The models that do not further alter a low-TC level imply that a slight improvement in overall mortality rate might be achieved if people with such levels make no further eating pattern changes or relax changes already made. The authors noted that individual efforts to actively increase a low TC value cannot be regarded as an appropriate strategy, and they are unlikely to undermine the current effective population strategy of gradually lowering TC. However, they were increasingly worried about the current heavy reliance on medications as a general means of lowering serum cholesterol, especially in women and the elderly. In their view, great scientific and health advances could be made, far in the future, from the study of blood and cell membrane lipids in non-atherosclerotic diseases. However, they maintained that the limited understanding of the mechanisms underlying the low-TC-disease associations should not be taken as an excuse for not taking action by public policy makers to keep blood TC values low.
As high serum TC concentration is crucial for the formation of arterial plaques, in its capacity as a principal risk factor in cardiovascular diseases, the effective strategy adopted by nutritional policy makers has been the concerted effort to reduce blood TC value. The observation that persistently low blood TC can be associated with antisocial behaviour, increased mortality from suicide, cancer, haemorrhagic stroke and other non-cardiovascular disease-related disorders, seems to run against the overall accepted belief. Arguments, such as those of Jacobs and Blackburn, have been advanced to play down the unwanted effects of reduced blood TC. One thing is clear though: the body has a need for cholesterol, which it obtains through absorption from the diet or from endogenous cellular synthesis. Under normal healthy conditions the body regulates the level of blood cholesterol within normal limits, and this controlling ability can be compromised by diabetes and cancer. There is the need for continuing the policy of maintaining blood TC values within the normal limits, provided there is the recognition that there are sub-groups of people whose blood TC is consistently below the normal. It is prudent not to reduce serum TC concentration to such an extent that it poses a health risk factor. Use of drugs as a means of reducing blood TC value is to be discouraged.
1 Freedman, D S; Byers, T; Barrett, D H; Stroup, N E; Eaker, E; Monroe-Blum, H (1995) Plasma lipid levels and psychologic characteristics in men. American Journal of Epidemiology 141: 507-517.
2 Muldoon, M F; Manuck, S B; Matthews, K A (1990) Lowering cholesterol concentration and mortality: a quantitative review of primary prevention trials. British Medical Journal 301: 309-314.
3 Konishi, M; Terao, A; Doi, M; Iida, M (1982) Osmotic resistance and cholesterol content of the erythrocyte membrane in cerebral hemorrhage. Igaki no Ayumi 120: 30-32 [in Japanese; cited by Jacobs and Blackburn].
4 Jacobs, D; Blackburn, H (1993) Models of effects of low blood cholesterol on public health: implications for practice and policy. Circulation 87: 1033-1036.
5 Manolio, T A; Ettinger, W H; Tracy, R P; Kuller, L H; Borhani, N O; Lynch, J C; Fried, L P (1993) Epidemiology of low cholesterol level in older adults. The cardiovascular Health Study. Circulation 87:728-737.
6 Wilson, T A; Nicolosi, R J (2002) Eggs and saturated fats: Role in atherosclerosis as shown by animal models. In Eggs and health Promotion: pp 111-122. Watson, R R, Iowa State Press.