The Japanese report
In April 2015 did four Japanese researchers, Tomohito Hamazaki, Harumi Okuyama, Yoichi Ogushi and Rokuro Hama, publish an analysis of several cholesterol studies in Japan and other countries. The 116 pages long report has a clear conclusion: Cholesterol is a friend, not an enemy.
The report is introduced with the following words:
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Heart disease

The Ibaraki Prefecture Health Study: A total of 30,802 men and 60,417 women were followed for 10.3 years. The figure shows relationship between LDL levels and the Hazard Ratio (HR) for all-cause mortality. Dark gray shading represents coronary heart disease (CHD) deaths. The width of each column is proportional to the number of participants in that group. The vertical lines represent 95% confidence intervals.
Comment: The study shows different patterns for men and women.
- Men: All-cause mortality is U-shaped, with lowest rate with LDL between 120 and 139 mg/dl. The highest mortality rate is when LDL is below 80 mg/dl. CHD (coronary heart disease) deaths increases slowly with LDL levels.
- Women: All-cause mortality for women decreases with increasing LDL levels. There's no correlation between CHD deaths and LDL levels.

Hazard ratios (HRs) for all-cause mortality and ischemic heart disease (IHD) according to total cholesterol level in Norway: HUNT 2 Study. A total of 52,087 Norwegians aged 20–74 years were followed to calculate cause-specific mortality for 10 years. HRs were adjusted for age, smoking, and systolic blood pressure. The height of the black bar denoting IHD deaths is set according to the ratio between the numbers of IHD deaths and all-cause deaths within the same column. HRs for IHD mortality in cholesterol categories II to IV were not significantly different from those in cholesterol category I in men or women. The width of each column is proportional to the number of participants in that group.
Comment: Both studies show that there is a correlation between low cholesterol and high all-cause mortality. This contradicts the 2015 guidelines for cholesterol levels set by the The other results are less conclusive when compared directly.
Aged people and heart disease
"Survival rate is definitely better in elderly people with high total or LDL cholesterol levels than in those with low levels. The proportion of people with FH or similar conditions among the elderly population is much smaller than that among younger populations, which explains why an inverse correlation between total cholesterol (or LDL cholesterol) and all-cause mortality becomes prominent with age in all countries. High LDL cholesterol levels might also be related to better cognitive function. The memory function of 193 functionally independent and community-dwelling elderly participants aged ≥80 years was cross-sectionally examined in the Key to Optimal Cognitive Aging ( KOCOA) Project, a prospective study undertaken in Okinawa, Japan. High LDL cholesterol levels and low triglyceride/HDL cholesterol ratios were associated with high Scenery Picture Memory Test scores after adjustment for many confounding factors. When viewed together with the data presented above on cholesterol and longevity, it seems clear that high cholesterol levels should not be considered unhealthy especially in elderly people." - Hamazaki, Okuyama, Ogushi and Hama
Stroke

Hazard ratio for stroke mortality in both men and women according to total cholesterol level. A total of 65,594 men and women in Japan aged 40– 89 years were followed for a mean 10.1 years. The width of each column is proportional to the number of participants. HR = Hazard ratio; CI = confidence interval.
Cancer
One of the biggest contributors to the inverse correlation between the lowest cholesterol levels and the highest all-cause mortality is cancer mortality.
Infectious disease
LDL and the other lipoproteins are the nonspecific frontline against a wide variety of infectious agents. Lipoproteins have long been known to bind to and inactivate bacteria, bacterial fragments (lipopolysaccharides, LPS), and viruses. The body can handle the entire phase of infection with a safety margin if lipoproteins neutralize a considerable proportion of toxic agents in blood. Without the buffer of lipoproteins, however, the immune system needs to deal with all the infection-related materials directly.
In a multiethnic cohort of 55,300 men and 65,271 women that was followed for 15 years (1979–1993), the association between total cholesterol and risk of infections (other than respiratory and HIV) was examined. Cholesterol was found to be inversely related to various infections, including all infections, in both sexes. The reduction of risk for all infections was 8% in both sexes.
Liver disease
Hazard ratios (HRs) for liver cancer and cirrhosis mortality according to low density lipoprotein (LDL) cholesterol level: Ibaraki Prefectural Health Study. A total of 16,217 participants aged 40–79 years (men: 34%) were followed for 14.1 years. The HRs for liver cancer and cirrhosis mortality were calculated using a multivariable Cox proportional hazards model. Covariates were age, sex, alanine transaminase, body mass index, alcohol intake, and smoking status. The height of the black bar denoting liver cirrhosis mortality is set according to the ratio between the numbers of cirrhosis deaths and total cancer + cirrhosis deaths. The width of each column is proportional to the number of participants. Note that zero mortality from liver cirrhosis was found in the group with LDL cholesterol ≥120 mg/dl (≥3.09 mmol/l).
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Hazard ratio (HR) for liver cancer incidence according to total cholesterol level in Korea: NHIC study in Korea. A total of 1,189,719 Korean adults enrolled in the National Health Insurance Corporation who underwent biennial medical examinations from 1992 through 1995 were observed for 14 years until cancer diagnosis or death. Cox’s proportional hazards models with attained age as the underlying time metric were used to calculate HRs with adjustment for smoking, alcohol consumption, body
mass index, physical activity, hypertension, and fasting serum glucose. The width of each column is proportional to the number of participants of that group; however, because of a limited number of women, the width of women’s columns is multiplied by 4. The trends in HRs for both sexes did not loose significance even after excluding cases during the first 10 years of observation.
Conclusion
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References
- Hamazaki, Okuyama, Ogushi and Hama: "Towards a paradigm shift in cholesterol treatment. A re-examination of the cholesterol issue in Japan".
- Journal of Clinical Lipidology: "National Lipid Association recommendations for patient-centered management of dyslipidemia " (2015).
- Nord-Trøndelag Heart Study (HUNT): Homepage.
- Hamazaki, Okuyama, Ogushi and Hama: "Towards a paradigm shift in cholesterol treatment. A re-examination of the cholesterol issue in Japan".
- Journal of Clinical Lipidology: "National Lipid Association recommendations for patient-centered management of dyslipidemia " (2015).
- Nord-Trøndelag Heart Study (HUNT): Homepage.