Background
In the mid 1800s, a German pathologist discovered that cholesterol was found in the artery walls of people who died from vascular diseases. From that time on, it was believed that cholesterol was responsible for the thickening of the arterial walls that lead to high blood pressure, increased risk of thickening of the arteries and blockages.
In the 1950s, the Framingham Heart Study resulted in the belief that there was a correlation between high blood cholesterol levels and coronary heart diseases. The Framingham study began in 1948 with 5,209 subjects. Prior to this study, almost nothing was known about the determinants of hypertensive or arteriosclerotic cardiovascular disease.
Much of the beliefs concerning cholesterol and heart disease today is based on this study from more than 70 years ago and with only 5,209 participants.
Merck Pharmaceuticals began clinical trials of a statin named lovastatin in April of 1980. The trials were stopped because trials with a drug structurally similar were stopped due to serious animal toxicity. For more on Merck, including lawsuits, see notes: Merck.
In 1983, Merck restarted the clinical trials on lovastatin. In September 1987, lovastatin became the first statin to be approved in the United States. Lovastatin went on to achieve an annual sales of more than $1 billion USD.
Simvastatin was approved in the U.S. in 1991. Approval of other statins followed: pravastatin in 1991, atorvastatin in 1997, cerivastatin in 1998, and rosuvastatin in 2003.
Influential pharmaceutical researchers began to monopolize the scientific debate on statins and pharmaceutical companies acquired all the data from the trials. They did not share this data. And, they only published trials that were favorable for statins.
“Late in the 20th century, the pharmaceutical industry started to exert powerful control over the evaluation of its prescription drugs by paying for clinical trials in their entirety and supporting all aspects of the work, including the logistics, data collection and analyses, and even ghost writing. As a result, data manipulation and misleading and/or false statements, including the concealment of results, were found one after another in the medical literature." (see notes: Pharmaceutical companies)
This domination and control, including what trials were published or not published, lasted for decades.
In a 2022 systematic review and meta-analysis of 21 statin trials involving 143,532 participants, the authors of the review found no relationship between lowering LDL cholesterol with statins and death, heart attack or stroke. They concluded that the benefits of statins were minimal, and that most of the trial participants who took statins derived no clinical benefit. (see notes: No benefit)
In the mid 1800s, a German pathologist discovered that cholesterol was found in the artery walls of people who died from vascular diseases. From that time on, it was believed that cholesterol was responsible for the thickening of the arterial walls that lead to high blood pressure, increased risk of thickening of the arteries and blockages.
In the 1950s, the Framingham Heart Study resulted in the belief that there was a correlation between high blood cholesterol levels and coronary heart diseases. The Framingham study began in 1948 with 5,209 subjects. Prior to this study, almost nothing was known about the determinants of hypertensive or arteriosclerotic cardiovascular disease.
Much of the beliefs concerning cholesterol and heart disease today is based on this study from more than 70 years ago and with only 5,209 participants.
Merck Pharmaceuticals began clinical trials of a statin named lovastatin in April of 1980. The trials were stopped because trials with a drug structurally similar were stopped due to serious animal toxicity. For more on Merck, including lawsuits, see notes: Merck.
In 1983, Merck restarted the clinical trials on lovastatin. In September 1987, lovastatin became the first statin to be approved in the United States. Lovastatin went on to achieve an annual sales of more than $1 billion USD.
Simvastatin was approved in the U.S. in 1991. Approval of other statins followed: pravastatin in 1991, atorvastatin in 1997, cerivastatin in 1998, and rosuvastatin in 2003.
Influential pharmaceutical researchers began to monopolize the scientific debate on statins and pharmaceutical companies acquired all the data from the trials. They did not share this data. And, they only published trials that were favorable for statins.
“Late in the 20th century, the pharmaceutical industry started to exert powerful control over the evaluation of its prescription drugs by paying for clinical trials in their entirety and supporting all aspects of the work, including the logistics, data collection and analyses, and even ghost writing. As a result, data manipulation and misleading and/or false statements, including the concealment of results, were found one after another in the medical literature." (see notes: Pharmaceutical companies)
This domination and control, including what trials were published or not published, lasted for decades.
In a 2022 systematic review and meta-analysis of 21 statin trials involving 143,532 participants, the authors of the review found no relationship between lowering LDL cholesterol with statins and death, heart attack or stroke. They concluded that the benefits of statins were minimal, and that most of the trial participants who took statins derived no clinical benefit. (see notes: No benefit)
Is LDL bad?
In a study with a total of 19,034 participants (see notes: LDL1), five groups were defined according to their LDL levels:
1. < 70
2. 70–99
3. 100–129
4. 130–159
5. ≥ 160 mg/dL
Results showed the fourth level of cholesterol, LDL between 130-159, had the lowest risk of cardiovascular mortality/death.
The group with the lowest level of LDL, less than 70, had a higher risk of cardiovascular mortality/death.
Another study showed similar results: the higher the LDL, the longer people lived and mortality/death was highest in the lowest cholesterol groups. (see notes: LDL2)
In a comprehensive review of cholesterol studies (see notes: LDL3), it was noted that if LDL was the cause of plaque in the arteries, we would see those people with high LDL with more atherosclerosis than people with low LDL. But instead, there was a lack of an association between LDL and degree of atherosclerosis.
The reviewers also pointed out a large study that included almost 140,000 patients with acute myocardial infarction. The patients' LDL at the time of admission to the hospital was lower than normal. In another study with the same findings, at the three year follow-up, total mortality/death among those with LDL below 105 mg/dl was twice as high compared to those with a higher LDL. (see notes: LDL3)
More studies: High LDL and longer life
In an article titled: High cholesterol may protect against infections and atherosclerosis (see: LDL4), authors looked at studies of elderly people where high cholesterol did not predict coronary morbidity or mortality/death. In fact, mortality was inversely associated with cholesterol — the higher the LDL, the longer the patients lived.
It was concluded that if high LDL were causal in coronary morbidity or death, the greatest effect should have been seen in patients with the highest LDL -- but that was not the case.
The conclusion was “high cholesterol predicts longevity rather than mortality in old people … The most likely explanation for these findings is that rather than promoting atherosclerosis, high cholesterol may be protective, possibly through its beneficial influence on the immune system.”
In an article titled: Low density lipoprotein cholesterol and all-cause mortality rate (see: LDL 5), lower LDL levels, being male, older age, being underweight, and the presence of diabetes were significant predictors for all-cause mortality/death. The survival rate was significantly lower for individuals with LDL levels that were very low (< 70 mg/dL) or low (93–143 mg/dL) compared with those with high LDL levels (≥ 144 mg/dL).
The conclusion was: There is an inverse relationship between LDL levels and the risk of all-cause mortality and this association is statistically significant. Having very low LDL levels (< 70) is predictive of higher all-cause mortality/death. (LDL5)
Another study looked at cohort studies with a total of 68,094 elderly people. Mortality/death was highest in those people with the lowest LDL. (see: elderly 1)
The study's conclusion: High LDL is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (that cholesterol, particularly LDL, is atherogenic). Since elderly people with high LDL live as long or longer than those with low LDL, our analysis provides reason to question the validity of the cholesterol hypothesis.
Results of yet another study reported that non-demented elderly with levels of total cholesterol and LDL in the lowest quartile were approximately twice as likely to die as those with the cholesterol levels in the highest quartile. Overall, women had higher lipid levels than men and lower mortality/death risk, but the risk of death was comparable for men and women compared to those with low lipid levels. (elderly 2)
The conclusion of that study was that low cholesterol is a robust predictor of mortality/death in the non-demented elderly. (elderly 2)
In a study with a total of 19,034 participants (see notes: LDL1), five groups were defined according to their LDL levels:
1. < 70
2. 70–99
3. 100–129
4. 130–159
5. ≥ 160 mg/dL
Results showed the fourth level of cholesterol, LDL between 130-159, had the lowest risk of cardiovascular mortality/death.
The group with the lowest level of LDL, less than 70, had a higher risk of cardiovascular mortality/death.
Another study showed similar results: the higher the LDL, the longer people lived and mortality/death was highest in the lowest cholesterol groups. (see notes: LDL2)
In a comprehensive review of cholesterol studies (see notes: LDL3), it was noted that if LDL was the cause of plaque in the arteries, we would see those people with high LDL with more atherosclerosis than people with low LDL. But instead, there was a lack of an association between LDL and degree of atherosclerosis.
The reviewers also pointed out a large study that included almost 140,000 patients with acute myocardial infarction. The patients' LDL at the time of admission to the hospital was lower than normal. In another study with the same findings, at the three year follow-up, total mortality/death among those with LDL below 105 mg/dl was twice as high compared to those with a higher LDL. (see notes: LDL3)
More studies: High LDL and longer life
In an article titled: High cholesterol may protect against infections and atherosclerosis (see: LDL4), authors looked at studies of elderly people where high cholesterol did not predict coronary morbidity or mortality/death. In fact, mortality was inversely associated with cholesterol — the higher the LDL, the longer the patients lived.
It was concluded that if high LDL were causal in coronary morbidity or death, the greatest effect should have been seen in patients with the highest LDL -- but that was not the case.
The conclusion was “high cholesterol predicts longevity rather than mortality in old people … The most likely explanation for these findings is that rather than promoting atherosclerosis, high cholesterol may be protective, possibly through its beneficial influence on the immune system.”
In an article titled: Low density lipoprotein cholesterol and all-cause mortality rate (see: LDL 5), lower LDL levels, being male, older age, being underweight, and the presence of diabetes were significant predictors for all-cause mortality/death. The survival rate was significantly lower for individuals with LDL levels that were very low (< 70 mg/dL) or low (93–143 mg/dL) compared with those with high LDL levels (≥ 144 mg/dL).
The conclusion was: There is an inverse relationship between LDL levels and the risk of all-cause mortality and this association is statistically significant. Having very low LDL levels (< 70) is predictive of higher all-cause mortality/death. (LDL5)
Another study looked at cohort studies with a total of 68,094 elderly people. Mortality/death was highest in those people with the lowest LDL. (see: elderly 1)
The study's conclusion: High LDL is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (that cholesterol, particularly LDL, is atherogenic). Since elderly people with high LDL live as long or longer than those with low LDL, our analysis provides reason to question the validity of the cholesterol hypothesis.
Results of yet another study reported that non-demented elderly with levels of total cholesterol and LDL in the lowest quartile were approximately twice as likely to die as those with the cholesterol levels in the highest quartile. Overall, women had higher lipid levels than men and lower mortality/death risk, but the risk of death was comparable for men and women compared to those with low lipid levels. (elderly 2)
The conclusion of that study was that low cholesterol is a robust predictor of mortality/death in the non-demented elderly. (elderly 2)
LDL Benefits
LDL cholesterol neutralizes bacteria and viruses. (see: LDL6, LDL7)
LDL cholesterol fights infection. (see: LDL6, LDL7, LDL8)
LDL protects against cancer. (see: LDL9)
LDL cholesterol neutralizes bacteria and viruses. (see: LDL6, LDL7)
LDL cholesterol fights infection. (see: LDL6, LDL7, LDL8)
LDL protects against cancer. (see: LDL9)
CoQ10 is produced naturally in the body, with the highest levels in the heart, liver, kidney and pancreas. It is a powerful antioxidant that protects your brain, heart and muscles. CoQ10 is in all cells of the body and is concentrated in the mitochondria, or the ‘powerhouse’ of the cell, which means it’s involved in energy production. CoQ10 also has anti-inflammatory properties. (see: Cleveland Clinic)
An analysis of seven studies concluded that CoQ10 could be beneficial for managing heart failure. (see: heart failure1)
Another review of 14 studies found that people with heart failure who took CoQ10 supplements had a decreased risk of dying and a greater improvement in exercise capacity compared to those who took a placebo. (heart fairlure2)
Since LDL carries CoQ10 to our muscles, this is partly why people on statins often have severe muscle pain and weakness.
Also, CoQ10 deficiency is common in many surviving stroke patients as they are mostly prescribed statins. (see: CoQ10 #1)
We also need DHEA ~~ which statins deplete.
The body makes DHEA on its own and then converts some DHEA to testosterone and estrogen, two powerful sex hormones needed for many different body functions beyond reproduction. These hormones are important for maintaining high energy levels, a strong metabolism, heart, brain and bone health.
DHEA boosts production of natural growth hormones that help build lean muscle mass and fight fat accumulation. Low DHEA levels cause many adults to experience weight gain, sluggishness, and lowered libido.
A Meta-analysis was performed on data from ten published studies that showed that statin treatment significantly reduces DHEA levels in women. (see: DHEA1)
In a study of 345 women and 464 men, the conclusion was that statin users have lower levels of DHEA. (see: DHEA2)
An analysis of seven studies concluded that CoQ10 could be beneficial for managing heart failure. (see: heart failure1)
Another review of 14 studies found that people with heart failure who took CoQ10 supplements had a decreased risk of dying and a greater improvement in exercise capacity compared to those who took a placebo. (heart fairlure2)
Since LDL carries CoQ10 to our muscles, this is partly why people on statins often have severe muscle pain and weakness.
Also, CoQ10 deficiency is common in many surviving stroke patients as they are mostly prescribed statins. (see: CoQ10 #1)
We also need DHEA ~~ which statins deplete.
The body makes DHEA on its own and then converts some DHEA to testosterone and estrogen, two powerful sex hormones needed for many different body functions beyond reproduction. These hormones are important for maintaining high energy levels, a strong metabolism, heart, brain and bone health.
DHEA boosts production of natural growth hormones that help build lean muscle mass and fight fat accumulation. Low DHEA levels cause many adults to experience weight gain, sluggishness, and lowered libido.
A Meta-analysis was performed on data from ten published studies that showed that statin treatment significantly reduces DHEA levels in women. (see: DHEA1)
In a study of 345 women and 464 men, the conclusion was that statin users have lower levels of DHEA. (see: DHEA2)
Lower and lower LDL levels are being stressed -- why?
In 1987, the emphasis was on lifestyle therapy (quit smoking, lose weight, etc.) for primary prevention of cardiovascular disease. At that time, use of cholesterol-lowering drugs was down-played. (see: LDL1)
In September 1987, lovastatin became the first statin to be approved in the U.S.
In 1993, emphasis was placed on "secondary" prevention (statins).
Recommendations for LDL cholesterol went from levels less than 130 in 1998 to less than 100 in 1993. (see: LDL3)
Previous attempts to maximally lower LDL levels with statins alone (via high dosage statins) were met with dejection due to the side effects of statins.
In 2001, more emphasis was added on high-risk prevention. At each successive guideline report, the intensity of LDL lowering therapy was increased and goals for LDL were lowered. The presence of cardiovascular disease of any type warranted an LDL goal of less than 100 mg/dL. (see: LDL4)
In 2004, guidelines underwent an update and the LDL goal was set of less than 70 mg/dL for patients deemed to be at very high risk for future cardiovascular events. (see: LDL5)
In 2018, guidelines included the reduction of LDL with high intensity statins or "maximally tolerated" statins to decrease cardiovascular risk. The goal was to reduce LDL by 50% and to consider adding ezetimibe to the maximally tolerated statins to achieve an LDL of less than 70.
The 2018 guidelines also state that if the goal of reducing LDL to less than 70 is not achieved, consider adding a PCSK9 inhibitor (evolocumab/brand name Repatha; alirocumab/brand name Praluent).
Also in the 2018 guidelines, for patients with severe hypercholesterolemia, the guidelines state: In patients with severe hypercholesterolemia (LDL ≥190), begin high intensity statin therapy (or moderate intensity statin + ezetimibe*) to achieve an LDL goal of less than 100. If this goal is not achieved, consider adding a PCSK9 inhibitor**.
* Side effects of ezetimibe: upper respiratory tract infections, muscle pain, abdominal pain, joint pain, diarrhea, tiredness, anaphylaxis, liver problems, depression and muscle breakdown.
** Side effects of PCSK9 inhibitors: limb pain, fatigue, mental confusion, difficulty focusing and neurocognitive issues.
In alirocumab trials, a PCSK9 inhibitor, 81% reported side effects. (see: Trials)
In a study that identified 33 lipid-lowering and 4 clinical outcome trials (Trials), it was found:
"The risk of myocardial infarction was not lower between the PCSK9 inhibitor and the placebo groups in the lipid-lowering trials and clinical outcomes trials. ...For heart failure, the risk was not lower in the PCSK9 inhibitor than the placebo groups."
Serious adverse events and deaths were reported in the trials on PCSK9 inhibitors. Evolocumab and alirocumab, the two PCSK9 inhibitors that are currently on the market, reduce LDL cholesterol by 53–59%. This has been shown in at least 25 trials that investigated the lipid-lowering effects of PCSK9 inhibitors. A meta-analysis did not show that PCSK9 inhibitors improve cardiovascular health. In fact, the analysis showed that evolocumab increased the risk of all-cause mortality. (Trials)
Ezetimibe inhibits the absorption of cholesterol from the small intestine and decreases the amount of cholesterol available to liver cells. We need cholesterol in our liver and our intestines. Cholesterol is vital to health and well-being. It is needed to make vitamin D, testosterone and estrogen and fat-dissolving bile acids.
Cholesterol production is so important that your liver and intestines make about 80% of the cholesterol you need to stay healthy. Cholesterol is found in every cell in the body. Only about 20% comes from the food you eat. (see: Harvard)
In 1987, the emphasis was on lifestyle therapy (quit smoking, lose weight, etc.) for primary prevention of cardiovascular disease. At that time, use of cholesterol-lowering drugs was down-played. (see: LDL1)
In September 1987, lovastatin became the first statin to be approved in the U.S.
In 1993, emphasis was placed on "secondary" prevention (statins).
Recommendations for LDL cholesterol went from levels less than 130 in 1998 to less than 100 in 1993. (see: LDL3)
Previous attempts to maximally lower LDL levels with statins alone (via high dosage statins) were met with dejection due to the side effects of statins.
In 2001, more emphasis was added on high-risk prevention. At each successive guideline report, the intensity of LDL lowering therapy was increased and goals for LDL were lowered. The presence of cardiovascular disease of any type warranted an LDL goal of less than 100 mg/dL. (see: LDL4)
In 2004, guidelines underwent an update and the LDL goal was set of less than 70 mg/dL for patients deemed to be at very high risk for future cardiovascular events. (see: LDL5)
In 2018, guidelines included the reduction of LDL with high intensity statins or "maximally tolerated" statins to decrease cardiovascular risk. The goal was to reduce LDL by 50% and to consider adding ezetimibe to the maximally tolerated statins to achieve an LDL of less than 70.
The 2018 guidelines also state that if the goal of reducing LDL to less than 70 is not achieved, consider adding a PCSK9 inhibitor (evolocumab/brand name Repatha; alirocumab/brand name Praluent).
Also in the 2018 guidelines, for patients with severe hypercholesterolemia, the guidelines state: In patients with severe hypercholesterolemia (LDL ≥190), begin high intensity statin therapy (or moderate intensity statin + ezetimibe*) to achieve an LDL goal of less than 100. If this goal is not achieved, consider adding a PCSK9 inhibitor**.
* Side effects of ezetimibe: upper respiratory tract infections, muscle pain, abdominal pain, joint pain, diarrhea, tiredness, anaphylaxis, liver problems, depression and muscle breakdown.
** Side effects of PCSK9 inhibitors: limb pain, fatigue, mental confusion, difficulty focusing and neurocognitive issues.
In alirocumab trials, a PCSK9 inhibitor, 81% reported side effects. (see: Trials)
In a study that identified 33 lipid-lowering and 4 clinical outcome trials (Trials), it was found:
"The risk of myocardial infarction was not lower between the PCSK9 inhibitor and the placebo groups in the lipid-lowering trials and clinical outcomes trials. ...For heart failure, the risk was not lower in the PCSK9 inhibitor than the placebo groups."
Serious adverse events and deaths were reported in the trials on PCSK9 inhibitors. Evolocumab and alirocumab, the two PCSK9 inhibitors that are currently on the market, reduce LDL cholesterol by 53–59%. This has been shown in at least 25 trials that investigated the lipid-lowering effects of PCSK9 inhibitors. A meta-analysis did not show that PCSK9 inhibitors improve cardiovascular health. In fact, the analysis showed that evolocumab increased the risk of all-cause mortality. (Trials)
Ezetimibe inhibits the absorption of cholesterol from the small intestine and decreases the amount of cholesterol available to liver cells. We need cholesterol in our liver and our intestines. Cholesterol is vital to health and well-being. It is needed to make vitamin D, testosterone and estrogen and fat-dissolving bile acids.
Cholesterol production is so important that your liver and intestines make about 80% of the cholesterol you need to stay healthy. Cholesterol is found in every cell in the body. Only about 20% comes from the food you eat. (see: Harvard)
Statins and cancer
Below are excerpts from: The statin-low cholesterol-cancer conundrum (see Notes: cancer1 )
“Four controlled, randomized statin trials have resulted in a statistically significant increase of cancer in the treatment group; and several case–control and cohort studies have also shown a significant risk of cancer associated with statins.
“Several cohort studies of healthy people have shown that low cholesterol is a risk marker for future cancer.
“… when searching Pubmed with the words ‘cancer AND cholesterol’ we identified nine cohort studies including more than 140,000 individuals, where cancer was inversely associated with cholesterol (i.e. low cholesterol=higher risk of cancer; higher cholesterol=lower risk of cancer) …
“In the first two simvastatin trials, cholesterol lowering increased non-melanoma skin cancer. Since these associations were not significant, the increase was attributed to chance. However, if the figures from both trials are calculated together, the difference between the treatment and control groups does become statistically significant.
“Cancer was also reported more often in the PROSPER trial (referring to a trial titled: Pravastatin in elderly individuals at risk of vascular disease). The difference was obvious after 1 year, and it increased steadily during the trial period to become statistically significant after 4 years.
“Cancer has been associated with statin treatment in several cohort and case–control studies as well. … Matsuzaki et al. followed 47,294 hypercholesterolemic Japanese patients on low dose (5–10 mg) simvastatin per day for 6 years and found that the number of cancer deaths was more than three times higher in patients whose total cholesterol was <160 mg/dl at follow-up compared with those whose cholesterol was normal or high.
“In a retrospective study of 388 men with prostate cancer and 1552 matched controls Chang et al. found an increasing cancer risk with increasing cumulative statin dose.
“In a case–control study by Agalliou et al., obese men taking statins had an increased risk of prostate cancer compared with obese non-users, with a stronger association for long-term use.
“A retrospective analysis by Ritch et al. found that among 1261 patients who had undergone radical prostatectomy, those on statins were more likely to have an elevation of biochemical tests that suggested recurrent cancer and also a more aggressive cancer type than non-users.
Below are excerpts from: The statin-low cholesterol-cancer conundrum (see Notes: cancer1 )
“Four controlled, randomized statin trials have resulted in a statistically significant increase of cancer in the treatment group; and several case–control and cohort studies have also shown a significant risk of cancer associated with statins.
“Several cohort studies of healthy people have shown that low cholesterol is a risk marker for future cancer.
“… when searching Pubmed with the words ‘cancer AND cholesterol’ we identified nine cohort studies including more than 140,000 individuals, where cancer was inversely associated with cholesterol (i.e. low cholesterol=higher risk of cancer; higher cholesterol=lower risk of cancer) …
“In the first two simvastatin trials, cholesterol lowering increased non-melanoma skin cancer. Since these associations were not significant, the increase was attributed to chance. However, if the figures from both trials are calculated together, the difference between the treatment and control groups does become statistically significant.
“Cancer was also reported more often in the PROSPER trial (referring to a trial titled: Pravastatin in elderly individuals at risk of vascular disease). The difference was obvious after 1 year, and it increased steadily during the trial period to become statistically significant after 4 years.
“Cancer has been associated with statin treatment in several cohort and case–control studies as well. … Matsuzaki et al. followed 47,294 hypercholesterolemic Japanese patients on low dose (5–10 mg) simvastatin per day for 6 years and found that the number of cancer deaths was more than three times higher in patients whose total cholesterol was <160 mg/dl at follow-up compared with those whose cholesterol was normal or high.
“In a retrospective study of 388 men with prostate cancer and 1552 matched controls Chang et al. found an increasing cancer risk with increasing cumulative statin dose.
“In a case–control study by Agalliou et al., obese men taking statins had an increased risk of prostate cancer compared with obese non-users, with a stronger association for long-term use.
“A retrospective analysis by Ritch et al. found that among 1261 patients who had undergone radical prostatectomy, those on statins were more likely to have an elevation of biochemical tests that suggested recurrent cancer and also a more aggressive cancer type than non-users.
In another study, which tested the association between low-density lipoprotein cholesterol (LDL), cardiovascular disease (CVD), cancer, and all-cause mortality in non-statin users, 347,971 subjects were tested. (see: cancer2)
Five groups were defined according to baseline LDL:
1. <70
2. 70–99
3. 100–129
4. 130–159
5. ≥160
A total of 2028 deaths occurred during follow-up. The lowest LDL cholesterol group (< 70) had a higher risk of all-cause mortality/death, CVD mortality/death, and cancer mortality/death compared to the reference group who had LDL cholesterol levels between 120–139.
In the validation cohort, 2338 deaths occurred during follow-up. The lowest LDL group (< 70) had a higher risk of all-cause mortality compared to the reference group. Low levels of LDL cholesterol were strongly and independently associated with increased risk of cancer, CVD, and all-cause mortality. (cancer2)
Five groups were defined according to baseline LDL:
1. <70
2. 70–99
3. 100–129
4. 130–159
5. ≥160
A total of 2028 deaths occurred during follow-up. The lowest LDL cholesterol group (< 70) had a higher risk of all-cause mortality/death, CVD mortality/death, and cancer mortality/death compared to the reference group who had LDL cholesterol levels between 120–139.
In the validation cohort, 2338 deaths occurred during follow-up. The lowest LDL group (< 70) had a higher risk of all-cause mortality compared to the reference group. Low levels of LDL cholesterol were strongly and independently associated with increased risk of cancer, CVD, and all-cause mortality. (cancer2)
Statins and Diabetes
A number of meta-analyses conducted in recent years have demonstrated an association between statins and diabetes. The following is from, Statin induced diabetes and its clinical implications. (see notes: diabetes1)
* A meta-analysis of five trials found a 13% increase in diabetes risk.
* Another included 13 randomized placebo controlled and standard care controlled trials with 91,140 participants. This meta-analysis demonstrated a 9% increased risk of incident diabetes.
* Another meta-analysis confirmed that statins have a diabetogenic effect and further concludes that this diabetogenic effect is dose dependent, with 12% higher risk on intensive-dose statin therapy. This meta-analysis included five statin trials with 32,752 participants without diabetes at baseline.
* In a meta-analysis of 17 randomized controlled trials, rosuvastatin (20 mg/day), atorvastatin (80 mg/day) and pravastatin (40 mg/day) were found to increase risk of new onset diabetes by 25%, 15% and 7%, respectively.
* In five statin trials with 32,752 participants without diabetes at baseline, 2749 developed diabetes. Of those, 1449 were assigned intensive-dose therapy and 1300 were assigned moderate-dose therapy. Conclusion: Intensive-dose statin therapy was associated with an increased risk of new-onset diabetes. (diabetes2)
A study titled, Statin users have an elevated risk of dysglycemia and new-onset-diabetes, had results showing a higher prevalence of elevated HbA1c occurring among non-diabetic users of statins. Additionally, statin users had a higher risk of developing new onset diabetes. Those taking statins for two years or longer were at the greatest risk of developing new onset diabetes. (diabetes3)
A number of meta-analyses conducted in recent years have demonstrated an association between statins and diabetes. The following is from, Statin induced diabetes and its clinical implications. (see notes: diabetes1)
* A meta-analysis of five trials found a 13% increase in diabetes risk.
* Another included 13 randomized placebo controlled and standard care controlled trials with 91,140 participants. This meta-analysis demonstrated a 9% increased risk of incident diabetes.
* Another meta-analysis confirmed that statins have a diabetogenic effect and further concludes that this diabetogenic effect is dose dependent, with 12% higher risk on intensive-dose statin therapy. This meta-analysis included five statin trials with 32,752 participants without diabetes at baseline.
* In a meta-analysis of 17 randomized controlled trials, rosuvastatin (20 mg/day), atorvastatin (80 mg/day) and pravastatin (40 mg/day) were found to increase risk of new onset diabetes by 25%, 15% and 7%, respectively.
* In five statin trials with 32,752 participants without diabetes at baseline, 2749 developed diabetes. Of those, 1449 were assigned intensive-dose therapy and 1300 were assigned moderate-dose therapy. Conclusion: Intensive-dose statin therapy was associated with an increased risk of new-onset diabetes. (diabetes2)
A study titled, Statin users have an elevated risk of dysglycemia and new-onset-diabetes, had results showing a higher prevalence of elevated HbA1c occurring among non-diabetic users of statins. Additionally, statin users had a higher risk of developing new onset diabetes. Those taking statins for two years or longer were at the greatest risk of developing new onset diabetes. (diabetes3)
Other dangers of statins
In a study titled, Statins stimulate atherosclerosis and heart failure, instead of finding cholesterol reduction resulting in decreased atherosclerosis, it was found that statins may be causative in coronary artery calcification and can impair muscle function in the heart and blood vessels. (other dangers1)
In that study, it was pointed out that statins inhibit the synthesis of vitamin K2, which takes part in protecting arteries from calcification. Statins also inhibit the biosynthesis of selenium containing proteins, one of which is glutathione, serving to suppress peroxidative stress. Authors note that "the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs."
In another study, it was found that among patients with early mild cognitive impairment and low to moderate serum cholesterol levels at the start, statin use was associated with more than double the risk of converting to dementia over eight years of follow-up compared with statin non-use. They also had a highly significant decline in metabolism of posterior cingulate cortex -- the region of the brain known to decline the most significantly in the earliest stages of Alzheimer’s disease. (other dangers2)
The following is from Annals of Nutrition and Metabolism, a leading international peer-reviewed journal. (see: otherdangers3)
Pg 88
Regarding statin use: There are "Important adverse effects involving the nervous system, carcinogenicity or diabetogenicity of statins. Breast cancer was recently reported to increase more than two-fold after 10 years of statin administration compared with non-use among participants with a history of high cholesterol levels only. Other adverse effects of statins include teratogenicity, depressed sexual pleasure, peripheral neuropathy, cataracts, musculoskeletal disturbance, and liver dysfunction."
Pg 91
Diminished Sexual Pleasure
"More than 1,000 adults with high levels LDL without heart disease were randomly assigned to either a statins group (simvastatin and pravastatin) or a placebo group and were followed for 6 months. Patients who took simvastatin had the largest LDL cholesterol decrease, but men in that subgroup experienced a nearly 50% reduction in sexual pleasure over the study period.
"Why would statins impair sexual pleasure? The sex-driving hormone testosterone is composed of cholesterol, the synthesis of which in the genital organs and adrenal glands is reduced by statins.
Liver Dysfunction
"High cholesterol levels are beneficial for severe liver disease. If liver damage by statins is serious, cholesterol levels may be markedly decreased by a compounding effect, namely, reduced cholesterol synthesis through the primary pharmacological effect of statins and liver damage, which also decreases cholesterol synthesis, as a side effect. And this compounding effect may start a vicious cycle."
In a study titled, Statins stimulate atherosclerosis and heart failure, instead of finding cholesterol reduction resulting in decreased atherosclerosis, it was found that statins may be causative in coronary artery calcification and can impair muscle function in the heart and blood vessels. (other dangers1)
In that study, it was pointed out that statins inhibit the synthesis of vitamin K2, which takes part in protecting arteries from calcification. Statins also inhibit the biosynthesis of selenium containing proteins, one of which is glutathione, serving to suppress peroxidative stress. Authors note that "the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs."
In another study, it was found that among patients with early mild cognitive impairment and low to moderate serum cholesterol levels at the start, statin use was associated with more than double the risk of converting to dementia over eight years of follow-up compared with statin non-use. They also had a highly significant decline in metabolism of posterior cingulate cortex -- the region of the brain known to decline the most significantly in the earliest stages of Alzheimer’s disease. (other dangers2)
The following is from Annals of Nutrition and Metabolism, a leading international peer-reviewed journal. (see: otherdangers3)
Pg 88
Regarding statin use: There are "Important adverse effects involving the nervous system, carcinogenicity or diabetogenicity of statins. Breast cancer was recently reported to increase more than two-fold after 10 years of statin administration compared with non-use among participants with a history of high cholesterol levels only. Other adverse effects of statins include teratogenicity, depressed sexual pleasure, peripheral neuropathy, cataracts, musculoskeletal disturbance, and liver dysfunction."
Pg 91
Diminished Sexual Pleasure
"More than 1,000 adults with high levels LDL without heart disease were randomly assigned to either a statins group (simvastatin and pravastatin) or a placebo group and were followed for 6 months. Patients who took simvastatin had the largest LDL cholesterol decrease, but men in that subgroup experienced a nearly 50% reduction in sexual pleasure over the study period.
"Why would statins impair sexual pleasure? The sex-driving hormone testosterone is composed of cholesterol, the synthesis of which in the genital organs and adrenal glands is reduced by statins.
Liver Dysfunction
"High cholesterol levels are beneficial for severe liver disease. If liver damage by statins is serious, cholesterol levels may be markedly decreased by a compounding effect, namely, reduced cholesterol synthesis through the primary pharmacological effect of statins and liver damage, which also decreases cholesterol synthesis, as a side effect. And this compounding effect may start a vicious cycle."
The excerpts below are taken from: LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature (see: Conclusion)
"During the years following the report of the Framingham Heart Study, numerous studies revealed that high total cholesterol (TC) is not associated with future cardiovascular disease (CVD) with the strongest evidence of a lack of relation between TC and CVD in elderly people.
"Today, the general opinion is that TC is not the most useful or accurate predictor of CVD, and interest has increasingly focused on low-density lipoprotein cholesterol (LDL-C).
"If LDL-C is atherogenic, people with high LDL-C should have more atherosclerosis than those with low LDL. At least four studies have shown a lack of an association between LDL-C and degree of atherosclerosis.
"If high LDL-C causes CVD, LDL-C of untreated patients with CVD should be higher than normal. However, in a large American study including almost 140,000 patients with acute myocardial infarction (AMI), their LDL-C at the time of admission to hospital was actually lower than normal.
"In another study with the same finding, the authors decided to lower the patients’ LDL-C even more, but at a follow-up 3 years later, total mortality among those with LDL-C below 105 mg/dl (2 mmol/l) was twice as high compared to those with a higher LDL-C.
" ... individuals with low LDL-C have a significantly increased risk of both infectious diseases and cancer..."
"If high LDL-C was the major cause of atherosclerosis and CVD, people with the highest LDL-C should have shorter lives than people with low values. However, in a recent systematic review of 19 cohort studies including more than 68,000 elderly people, we found the opposite.
"In the largest cohort study, those with the highest LDL-C levels lived even longer than those on statin treatment. In addition, numerous Japanese studies have found that high LDL-C is not a risk factor for CHD mortality in women of any age.
"Furthermore ... an increase of life expectancy has never been mentioned in any cholesterol-lowering trial, but as calculated recently by Kristensen et al., statin treatment does not prolong lifespan by more than an average of a few days."
"During the years following the report of the Framingham Heart Study, numerous studies revealed that high total cholesterol (TC) is not associated with future cardiovascular disease (CVD) with the strongest evidence of a lack of relation between TC and CVD in elderly people.
"Today, the general opinion is that TC is not the most useful or accurate predictor of CVD, and interest has increasingly focused on low-density lipoprotein cholesterol (LDL-C).
"If LDL-C is atherogenic, people with high LDL-C should have more atherosclerosis than those with low LDL. At least four studies have shown a lack of an association between LDL-C and degree of atherosclerosis.
"If high LDL-C causes CVD, LDL-C of untreated patients with CVD should be higher than normal. However, in a large American study including almost 140,000 patients with acute myocardial infarction (AMI), their LDL-C at the time of admission to hospital was actually lower than normal.
"In another study with the same finding, the authors decided to lower the patients’ LDL-C even more, but at a follow-up 3 years later, total mortality among those with LDL-C below 105 mg/dl (2 mmol/l) was twice as high compared to those with a higher LDL-C.
" ... individuals with low LDL-C have a significantly increased risk of both infectious diseases and cancer..."
"If high LDL-C was the major cause of atherosclerosis and CVD, people with the highest LDL-C should have shorter lives than people with low values. However, in a recent systematic review of 19 cohort studies including more than 68,000 elderly people, we found the opposite.
"In the largest cohort study, those with the highest LDL-C levels lived even longer than those on statin treatment. In addition, numerous Japanese studies have found that high LDL-C is not a risk factor for CHD mortality in women of any age.
"Furthermore ... an increase of life expectancy has never been mentioned in any cholesterol-lowering trial, but as calculated recently by Kristensen et al., statin treatment does not prolong lifespan by more than an average of a few days."
Notes
Cancer
1. The statin-low cholesterol-cancer conundrum
https://academic.oup.com/qjmed/article/105/4/383/1554800?login=false
2. Low Levels of Low-Density Lipoprotein Cholesterol and Mortality Outcomes in Non-Statin Users
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832139/
1. The statin-low cholesterol-cancer conundrum
https://academic.oup.com/qjmed/article/105/4/383/1554800?login=false
2. Low Levels of Low-Density Lipoprotein Cholesterol and Mortality Outcomes in Non-Statin Users
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832139/
CoQ10
1. Coenzyme Q10 supplementation improves acute outcomes of stroke in rats pretreated with atorvastatin
https://www.tandfonline.com/doi/abs/10.1080/1028415X.2017.1376928
2. Coenzyme Q10 in essential hypertension
https://www.sciencedirect.com/science/article/abs/pii/0098299794900361
3. Coenzyme Q10 for heart failure
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092430/
4. Role of Coenzyme Q10 in Prophylaxis of Myocardial Infarction
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935267/
5. Statin therapy and plasma coenzyme Q10 concentrations--A systematic review and meta-analysis of placebo-controlled trials
https://www.sciencedirect.com/science/article/abs/pii/S1043661815001413?via%3Dihub
1. Coenzyme Q10 supplementation improves acute outcomes of stroke in rats pretreated with atorvastatin
https://www.tandfonline.com/doi/abs/10.1080/1028415X.2017.1376928
2. Coenzyme Q10 in essential hypertension
https://www.sciencedirect.com/science/article/abs/pii/0098299794900361
3. Coenzyme Q10 for heart failure
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092430/
4. Role of Coenzyme Q10 in Prophylaxis of Myocardial Infarction
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935267/
5. Statin therapy and plasma coenzyme Q10 concentrations--A systematic review and meta-analysis of placebo-controlled trials
https://www.sciencedirect.com/science/article/abs/pii/S1043661815001413?via%3Dihub
Conclusion
LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature
https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1519391
LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature
https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1519391
DHEA
1. The Effect of Statins on Levels of Dehydroepiandrosterone (DHEA) in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348753/
2. Association Between Statin Use and Sex Hormone in the Multi-Ethnic Study of Atherosclerosis Cohort
https://academic.oup.com/jcem/article/104/10/4600/5509372?login=false
1. The Effect of Statins on Levels of Dehydroepiandrosterone (DHEA) in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348753/
2. Association Between Statin Use and Sex Hormone in the Multi-Ethnic Study of Atherosclerosis Cohort
https://academic.oup.com/jcem/article/104/10/4600/5509372?login=false
Diabetes
1. Statin induced diabetes and its clinical implications
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156828/#ref10
2. Statin users have an elevated risk of dysglycemia and new-onset-diabetes
https://onlinelibrary.wiley.com/doi/abs/10.1002/dmrr.3189
1. Statin induced diabetes and its clinical implications
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156828/#ref10
2. Statin users have an elevated risk of dysglycemia and new-onset-diabetes
https://onlinelibrary.wiley.com/doi/abs/10.1002/dmrr.3189
Elderly
1. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review
https://bmjopen.bmj.com/content/6/6/e010401
https://dash.harvard.edu/bitstream/handle/1/27662088/4908872.pdf?sequence=1&isAllowed=y
2. Relationship between plasma lipids and all-cause mortality in nondemented elderly
https://pubmed.ncbi.nlm.nih.gov/15673344/
1. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review
https://bmjopen.bmj.com/content/6/6/e010401
https://dash.harvard.edu/bitstream/handle/1/27662088/4908872.pdf?sequence=1&isAllowed=y
2. Relationship between plasma lipids and all-cause mortality in nondemented elderly
https://pubmed.ncbi.nlm.nih.gov/15673344/
Guidelines for the Management of High Blood Cholesterol
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937425/
https://www.ncbi.nlm.nih.gov/books/NBK305897/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937425/
https://www.ncbi.nlm.nih.gov/books/NBK305897/
Harvard
Cholesterol production in your body
https://www.health.harvard.edu/heart-health/how-its-made-cholesterol-production-in-your-body
Cholesterol production in your body
https://www.health.harvard.edu/heart-health/how-its-made-cholesterol-production-in-your-body
Heart Failure
1. Coenzyme Q10 in the treatment of heart failure: A systematic review of systematic reviews
www.ncbi.nlm.nih.gov/pmc/articles/PMC6097169/
2. Efficacy of coenzyme Q10 in patients with cardiac failure: a meta-analysis of clinical trials
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525208/
1. Coenzyme Q10 in the treatment of heart failure: A systematic review of systematic reviews
www.ncbi.nlm.nih.gov/pmc/articles/PMC6097169/
2. Efficacy of coenzyme Q10 in patients with cardiac failure: a meta-analysis of clinical trials
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525208/
LDL
1. Association between low density lipoprotein cholesterol and all-cause mortality: results from the NHANES 1999–2014
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586008/
2. Towards a Paradigm Shift in Cholesterol Treatment, page 3-9
https://karger.com/anm/article-pdf/66/Suppl.%204/1/2183714/000381654.pdf
3. LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature
https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1519391
4. High cholesterol may protect against infections and atherosclerosis
https://academic.oup.com/qjmed/article/96/12/927/1533176?login=false
5. Low density lipoprotein cholesterol and all-cause mortality rate
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436563/
Key points: If high total-C or LDL-C were the most important cause of cardiovascular disease, it should be a risk factor in both sexes, in all populations, and in all age groups. But in many populations, the association between t-C and mortality is absent or inverse; or increasing t-C is associated with low coronary and total mortality.
6. Lipids: a key player in the battle between the host and microorganisms
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494250/
Key points: It is now recognized that lipids and lipoproteins play an important role in host defense as part of the innate immune system. For example, lipoproteins including HDL, chylomicrons, VLDL, and LDL can bind and neutralize LPS (products of gram negative bacteria), lipoteichoic acid, and viruses.
Studies have shown that HDL may inhibit the ability of certain viruses to penetrate cells.
Lipoproteins can block the adhesion of bacteria to host cells and reduce tissue invasion.
Lipoproteins have been shown to play an important role in defending against parasitic infections.
In addition to their transport functions, there is abundant evidence that lipoproteins and lipids protect the host from the toxic effects of microorganisms.
7. Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024721/
Key points: Research shows that lipid rafts and lipoprotein interactions are not only essential in the pathogenesis of infectious disease, but also in the compensatory immune response to ameliorate infection.
Overall, it is clear that cholesterol metabolism plays an important role in the regulation of immunity and inflammatory disease risk.
Research from animal and human studies further demonstrates that cholesterol-rich dietary patterns differentially impact pathophysiology and clinical outcomes of distinct infectious diseases by various bacterial and viral pathogens, and that dietary cholesterol may either exasperate or mitigate autoimmune dysfunction.
8. Plasma lipoproteins are important components of the immune system
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1348-0421.2009.00203.x
Key points:
Plasma lipoproteins (VLDL, LDL, Lp[a] and HDL) function primarily in lipid transport among tissues and organs. Evidence suggests that lipoproteins may also prevent bacterial, viral and parasitic infections and are therefore a component of innate immunity.
Lipoproteins participate in innate immunity since they have broad preventive effects against bacterial, viral and parasitic infections.
9. Low LDL chlesterol is related to cancer risk
https://www.acc.org/about-acc/press-releases/2012/03/25/15/15/ldl_cancer
Key points: Previous studies of cholesterol-lowering drugs have suggested a strong association between low levels of LDL-C and cancer risk. This is the first study to examine the relationship of low LDL-C and cancer risk over an extended period of time.
Researchers found that LDL cholesterol values were lower in cancer subjects than matched controls at each point of assessment throughout an average of 18.7 years prior to diagnosis.
1. Association between low density lipoprotein cholesterol and all-cause mortality: results from the NHANES 1999–2014
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586008/
2. Towards a Paradigm Shift in Cholesterol Treatment, page 3-9
https://karger.com/anm/article-pdf/66/Suppl.%204/1/2183714/000381654.pdf
3. LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature
https://www.tandfonline.com/doi/full/10.1080/17512433.2018.1519391
4. High cholesterol may protect against infections and atherosclerosis
https://academic.oup.com/qjmed/article/96/12/927/1533176?login=false
5. Low density lipoprotein cholesterol and all-cause mortality rate
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436563/
Key points: If high total-C or LDL-C were the most important cause of cardiovascular disease, it should be a risk factor in both sexes, in all populations, and in all age groups. But in many populations, the association between t-C and mortality is absent or inverse; or increasing t-C is associated with low coronary and total mortality.
6. Lipids: a key player in the battle between the host and microorganisms
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494250/
Key points: It is now recognized that lipids and lipoproteins play an important role in host defense as part of the innate immune system. For example, lipoproteins including HDL, chylomicrons, VLDL, and LDL can bind and neutralize LPS (products of gram negative bacteria), lipoteichoic acid, and viruses.
Studies have shown that HDL may inhibit the ability of certain viruses to penetrate cells.
Lipoproteins can block the adhesion of bacteria to host cells and reduce tissue invasion.
Lipoproteins have been shown to play an important role in defending against parasitic infections.
In addition to their transport functions, there is abundant evidence that lipoproteins and lipids protect the host from the toxic effects of microorganisms.
7. Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024721/
Key points: Research shows that lipid rafts and lipoprotein interactions are not only essential in the pathogenesis of infectious disease, but also in the compensatory immune response to ameliorate infection.
Overall, it is clear that cholesterol metabolism plays an important role in the regulation of immunity and inflammatory disease risk.
Research from animal and human studies further demonstrates that cholesterol-rich dietary patterns differentially impact pathophysiology and clinical outcomes of distinct infectious diseases by various bacterial and viral pathogens, and that dietary cholesterol may either exasperate or mitigate autoimmune dysfunction.
8. Plasma lipoproteins are important components of the immune system
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1348-0421.2009.00203.x
Key points:
Plasma lipoproteins (VLDL, LDL, Lp[a] and HDL) function primarily in lipid transport among tissues and organs. Evidence suggests that lipoproteins may also prevent bacterial, viral and parasitic infections and are therefore a component of innate immunity.
Lipoproteins participate in innate immunity since they have broad preventive effects against bacterial, viral and parasitic infections.
9. Low LDL chlesterol is related to cancer risk
https://www.acc.org/about-acc/press-releases/2012/03/25/15/15/ldl_cancer
Key points: Previous studies of cholesterol-lowering drugs have suggested a strong association between low levels of LDL-C and cancer risk. This is the first study to examine the relationship of low LDL-C and cancer risk over an extended period of time.
Researchers found that LDL cholesterol values were lower in cancer subjects than matched controls at each point of assessment throughout an average of 18.7 years prior to diagnosis.
Merck
The company develops vaccines, biologic therapies and other products.
In 2020, the company had 6 blockbuster drugs, each with over $1 billion in revenue: Keytruda (pembrolizumab), a humanized antibody used in cancer immunotherapy that had $14.3 billion in 2020 revenue; Januvia (sitagliptin), an anti-diabetic medication used to treat type 2 diabetes that had $5.3 billion in 2020 revenue; Gardasil, an HPV vaccine that had $3.9 billion in 2020 revenue; Varivax, a varicella vaccine used to protect against chickenpox that had $1.9 billion in 2020 revenues; Bridion (Sugammadex), a neuromuscular-blocking drug that had $1.2 billion in 2020 revenue; and Pneumovax 23, a pneumococcal polysaccharide vaccine that had $1.1 billion in 2020 revenue.
Other major products by the company include Isentress (raltegravir), an antiretroviral medication used to treat HIV/AIDS that had $857 million in 2020 revenue; Simponi (golimumab), a human monoclonal antibody used as an immunosuppressive drug that had $838 million in 2020 revenue; RotaTeq, a rotavirus vaccine that had $797 million in 2020 revenue; and Lynparza (olaparib), a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults that generated $725 million in 2020 revenue for the company.[1]
In 1953, Merck & Co. merged with Philadelphia-based Sharp & Dohme, Inc., becoming the largest U.S. drugmaker. Sharp and Dohme had acquired H. K. Mulford Company in 1929, adding smallpox vaccines to its portfolio. The combined company kept the trade name Merck in the United States and Canada, and as Merck Sharp & Dohme (MSD) outside North America.
Maurice Hilleman, a scientist at Merck, developed the first mumps vaccine in 1967, the first rubella vaccine in 1969, and the first trivalent measles, mumps, rubella (MMR vaccine) in 1971. Hilleman also developed the first Hepatitis B vaccine and the first varicella vaccine, for chickenpox.
In 1982, the company formed a joint venture, KBI Inc., with AstraZeneca. During the late 1980s and 1990s, the company also established joint ventures with DuPont to access research and development expertise, and with Johnson & Johnson to sell over-the-counter consumer medications.
In May 2002, The Bill & Melinda Gates Foundation purchased stock in Merck.
Lawsuits
Vioxx
In 1999, the U.S. Food and Drug Administration (FDA) approved Vioxx, a Merck product for treating arthritis.
Vioxx became one of the most prescribed drugs in history.
Thereafter, studies by Merck and by others found an increased risk of heart attack associated with Vioxx use.
On September 23, 2004, Merck received information about results from a clinical trial it was conducting that included findings of increased risk of heart attacks among Vioxx users who had been using the medication for over eighteen months.
An analysis for the period 1999–2004, reported that Vioxx was associated with 46,783 heart attacks, and along with the other popular drug, Celebrex, an estimated 26,603 deaths from both.
About 50,000 people sued Merck, claiming they or their family members had suffered medical problems such as heart attacks or strokes after taking Vioxx.
According to internal e-mail traffic released at a later lawsuit, Merck had a list of doctors critical of Vioxx to be "neutralized" or "discredited". "We may need to seek them out and destroy them where they live," wrote an employee. A Stanford Medical School professor said that Merck was engaged in intimidation of researchers and infringement upon academic freedom.
Propecia
In 2021, an investigation revealed that Merck's baldness drug Propecia caused persistent sexual dysfunction in men. The drug has been linked to over 700 incidences of suicidal thoughts and 110 deaths. Merck has been receiving reports since 1998, but never included the risks on the label.
In 2015, Merck was sued by consumer-rights law firm Hagens Berman over a wrongful death linked to Propecia.[185]
The company develops vaccines, biologic therapies and other products.
In 2020, the company had 6 blockbuster drugs, each with over $1 billion in revenue: Keytruda (pembrolizumab), a humanized antibody used in cancer immunotherapy that had $14.3 billion in 2020 revenue; Januvia (sitagliptin), an anti-diabetic medication used to treat type 2 diabetes that had $5.3 billion in 2020 revenue; Gardasil, an HPV vaccine that had $3.9 billion in 2020 revenue; Varivax, a varicella vaccine used to protect against chickenpox that had $1.9 billion in 2020 revenues; Bridion (Sugammadex), a neuromuscular-blocking drug that had $1.2 billion in 2020 revenue; and Pneumovax 23, a pneumococcal polysaccharide vaccine that had $1.1 billion in 2020 revenue.
Other major products by the company include Isentress (raltegravir), an antiretroviral medication used to treat HIV/AIDS that had $857 million in 2020 revenue; Simponi (golimumab), a human monoclonal antibody used as an immunosuppressive drug that had $838 million in 2020 revenue; RotaTeq, a rotavirus vaccine that had $797 million in 2020 revenue; and Lynparza (olaparib), a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults that generated $725 million in 2020 revenue for the company.[1]
In 1953, Merck & Co. merged with Philadelphia-based Sharp & Dohme, Inc., becoming the largest U.S. drugmaker. Sharp and Dohme had acquired H. K. Mulford Company in 1929, adding smallpox vaccines to its portfolio. The combined company kept the trade name Merck in the United States and Canada, and as Merck Sharp & Dohme (MSD) outside North America.
Maurice Hilleman, a scientist at Merck, developed the first mumps vaccine in 1967, the first rubella vaccine in 1969, and the first trivalent measles, mumps, rubella (MMR vaccine) in 1971. Hilleman also developed the first Hepatitis B vaccine and the first varicella vaccine, for chickenpox.
In 1982, the company formed a joint venture, KBI Inc., with AstraZeneca. During the late 1980s and 1990s, the company also established joint ventures with DuPont to access research and development expertise, and with Johnson & Johnson to sell over-the-counter consumer medications.
In May 2002, The Bill & Melinda Gates Foundation purchased stock in Merck.
Lawsuits
Vioxx
In 1999, the U.S. Food and Drug Administration (FDA) approved Vioxx, a Merck product for treating arthritis.
Vioxx became one of the most prescribed drugs in history.
Thereafter, studies by Merck and by others found an increased risk of heart attack associated with Vioxx use.
On September 23, 2004, Merck received information about results from a clinical trial it was conducting that included findings of increased risk of heart attacks among Vioxx users who had been using the medication for over eighteen months.
An analysis for the period 1999–2004, reported that Vioxx was associated with 46,783 heart attacks, and along with the other popular drug, Celebrex, an estimated 26,603 deaths from both.
About 50,000 people sued Merck, claiming they or their family members had suffered medical problems such as heart attacks or strokes after taking Vioxx.
According to internal e-mail traffic released at a later lawsuit, Merck had a list of doctors critical of Vioxx to be "neutralized" or "discredited". "We may need to seek them out and destroy them where they live," wrote an employee. A Stanford Medical School professor said that Merck was engaged in intimidation of researchers and infringement upon academic freedom.
Propecia
In 2021, an investigation revealed that Merck's baldness drug Propecia caused persistent sexual dysfunction in men. The drug has been linked to over 700 incidences of suicidal thoughts and 110 deaths. Merck has been receiving reports since 1998, but never included the risks on the label.
In 2015, Merck was sued by consumer-rights law firm Hagens Berman over a wrongful death linked to Propecia.[185]
No Benefit
Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2790055
This analysis also highlighted the significant difference in the relative risk reduction (RRR) and absolute risk reduction (ARR) of statin therapy on death, heart attack and stroke. For example, if your baseline risk of having a heart attack is 2% and taking a drug reduces that risk to 1%, then in relative terms you halved your risk (50% RRR) which sounds impressive, but in absolute terms, you have only reduced your risk by 1% (ARR).
Our analysis showed that trial participants taking a statin for an average of 4.4 years, showed a 29% RRR in heart attacks, but the ARR was only 1.3%.
If this is not effectively communicated to a patient, can they make a fully informed decision about their treatment?
It may also influence their calculated benefit:harm ratio if the patient is experiencing debilitating effects from the medication.
Bottom line:
This systematic review and meta-analysis on 21 statin trials involving 143,532 participants found no consistent relationship between lowering LDL-C and death, heart attack or stroke, following statin therapy.
Doctors are not effectively and transparently communicating cardiovascular risk to their patients, thereby not allowing informed decision-making.
We concluded that the benefits of statins were minimal, and most of the trial participants who took statins, derived no clinical benefit.
Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2790055
This analysis also highlighted the significant difference in the relative risk reduction (RRR) and absolute risk reduction (ARR) of statin therapy on death, heart attack and stroke. For example, if your baseline risk of having a heart attack is 2% and taking a drug reduces that risk to 1%, then in relative terms you halved your risk (50% RRR) which sounds impressive, but in absolute terms, you have only reduced your risk by 1% (ARR).
Our analysis showed that trial participants taking a statin for an average of 4.4 years, showed a 29% RRR in heart attacks, but the ARR was only 1.3%.
If this is not effectively communicated to a patient, can they make a fully informed decision about their treatment?
It may also influence their calculated benefit:harm ratio if the patient is experiencing debilitating effects from the medication.
Bottom line:
This systematic review and meta-analysis on 21 statin trials involving 143,532 participants found no consistent relationship between lowering LDL-C and death, heart attack or stroke, following statin therapy.
Doctors are not effectively and transparently communicating cardiovascular risk to their patients, thereby not allowing informed decision-making.
We concluded that the benefits of statins were minimal, and most of the trial participants who took statins, derived no clinical benefit.
Other Dangers
1. Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms
https://pubmed.ncbi.nlm.nih.gov/25655639/
2. Lipophilic Statins in Subjects with Early Mild Cognitive Impairment: Associations with Conversion to Dementia and Decline in Posterior Cingulate Brain Metabolism
https://jnm.snmjournals.org/content/62/supplement_1/102
3. The Latest Edition of the JAS Guidelines (2012) Part IV From Ann Nutr Metab 2015;66(suppl 4):1-116
https://karger.com/anm/article-pdf/66/Suppl.%204/1/2183714/000381654.pdf
1. Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms
https://pubmed.ncbi.nlm.nih.gov/25655639/
2. Lipophilic Statins in Subjects with Early Mild Cognitive Impairment: Associations with Conversion to Dementia and Decline in Posterior Cingulate Brain Metabolism
https://jnm.snmjournals.org/content/62/supplement_1/102
3. The Latest Edition of the JAS Guidelines (2012) Part IV From Ann Nutr Metab 2015;66(suppl 4):1-116
https://karger.com/anm/article-pdf/66/Suppl.%204/1/2183714/000381654.pdf
Pharmaceutical Companies
The Latest Edition of thee JAS Guidelines (2012) Part IV. From Ann Nutr Metab 2015;66(suppl 4):1-116
https://karger.com/anm/article-pdf/66/Suppl.%204/1/2183714/000381654.pdf
Pg 99-100
“Late in the 20th century, the pharmaceutical industry started to exert powerful control over the evaluation of its prescription drugs by paying for clinical trials in their entirety and supporting all aspects of the work, including the logistics, data collection and analyses, and even ghost writing [11]. As a result, data manipulation and misleading and/or false statements, including the concealment of results, were found one after another in the medical literature. The Vioxx scandal prompted a change. In 2004, Merck withdrew the medication Vioxx from the market because of concerns about increased risks for heart attack and stroke; however, the company had kept it on the market although it very likely had known about these risks for 5 years[12].”
11 Ross JS, Hill KP, Egilman DS, Krumholz HM: Guest authorship and ghostwriting in publications related to rofecoxib: a case study of industry documents from rofecoxib litigaion. JAMA 2008;299:1800–1812.
12 Reuters (New York). Merck agrees to pay $4.85 billion in Vioxx settlement. Available online at: http://wwwreuterscom/article/2007/11/10/businesspro-merck-vioxx-settlement-dc-idUSL0929726620071110
(accessed April 22, 2014). Nov 9, 2007.
The Latest Edition of thee JAS Guidelines (2012) Part IV. From Ann Nutr Metab 2015;66(suppl 4):1-116
https://karger.com/anm/article-pdf/66/Suppl.%204/1/2183714/000381654.pdf
Pg 99-100
“Late in the 20th century, the pharmaceutical industry started to exert powerful control over the evaluation of its prescription drugs by paying for clinical trials in their entirety and supporting all aspects of the work, including the logistics, data collection and analyses, and even ghost writing [11]. As a result, data manipulation and misleading and/or false statements, including the concealment of results, were found one after another in the medical literature. The Vioxx scandal prompted a change. In 2004, Merck withdrew the medication Vioxx from the market because of concerns about increased risks for heart attack and stroke; however, the company had kept it on the market although it very likely had known about these risks for 5 years[12].”
11 Ross JS, Hill KP, Egilman DS, Krumholz HM: Guest authorship and ghostwriting in publications related to rofecoxib: a case study of industry documents from rofecoxib litigaion. JAMA 2008;299:1800–1812.
12 Reuters (New York). Merck agrees to pay $4.85 billion in Vioxx settlement. Available online at: http://wwwreuterscom/article/2007/11/10/businesspro-merck-vioxx-settlement-dc-idUSL0929726620071110
(accessed April 22, 2014). Nov 9, 2007.
Trials
Serious adverse events and deaths in PCSK9 inhibitor trials reported on ClinicalTrials.gov: a systematic review
https://www.tandfonline.com/doi/full/10.1080/17512433.2020.1787832
Serious adverse events and deaths in PCSK9 inhibitor trials reported on ClinicalTrials.gov: a systematic review
https://www.tandfonline.com/doi/full/10.1080/17512433.2020.1787832
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