Familial hypercholesterolemia alternative treatment, natural therapy, vitamins, supplements, herbs
April 20 2016

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that clinically leads to increased low density lipoprotein-cholesterol (LDL-C) levels. As a consequence, FH patients are at high risk for cardiovascular disease and stroke. FH affects about 1 in 250 adults in the United States. There are two clinical manifestations: the milder heterozygous form and more severe homozygous form.

The challenges of using statins to treat FH, are there natural alternatives?
Although statin medication treatment lowers cholesterol levels in those with FH, does this ultimately result in increased longevity in those whose treatment starts in their 20s, 30s, or 40s? Or do the side effects and adverse reactions from long term statin use for several decades negate the benefits of lowering high cholesterol levels? The answer to this important question remains to be determined. It is also possible that statin use reduces the risk for heart disease and stroke but causes other health problems reducing quality of life. These problems include low mood, tiredness, lack of motivation, muscle and joint aches, and various other statin-associated issues.
   In lieu of this dilemma, it is difficult to make recommendations. My advice, for the time being, is to do everything possible in terms of lifestyle and dietary choices to lead a heart healthy life (see the cholesterol link above), and to use statin drugs in the lowest dose possible, perhaps at times taking breaks from use.
   Is it possible to avoid the use of prescription medications and rely exclusively on diet, exercise, and the use of dietary supplements that lower cholesterol levels and improve blood vessel health and reduce the risk for heart disease and stroke? Maybe. Probably.

Curr Opin Lipidol. 2015. The hinterland of familial hypercholesterolaemia: what do we not know? Familial hypercholesterolaemia is the commonest autosomal dominant disorder in man, but many questions about familial hypercholesterolaemia remain to be answered. Familial hypercholesterolaemia is commoner than previously thought, but its epidemiology needs further investigation against a background of changing environmental and lifestyle factors that may bear on its phenotypic expression. Despite familial hypercholesterolaemia being a common genetic condition, aspects of basic epidemiology, risk assessment, treatment, and models of care remain uncertain.

Natural treatment options and alternatives, there are probably many other options besides the ones studied here
Am J Cardiol. 2015. Usefulness of Nutraceuticals (Armolipid Plus) Versus Ezetimibe and Combination in Statin-Intolerant Patients With Dyslipidemia With Coronary Heart Disease. tatins are extensively used to treat dyslipidemia, but, because of their low tolerability profile, they are discontinued in a significant proportion of patients. Ezetimibe and nutraceuticals have been introduced as alternative therapies and have proved to be effective and well tolerated. A single-blind, single-center, randomized, prospective, and parallel group trial comparing a combination of nutraceuticals (red yeast rice, policosanol, berberine, folic acid, coenzyme Q10 and astaxanthin), called Armolipid Plus, and ezetimibe for 3 months in terms of efficacy and tolerability. Patients who did not achieve their therapeutic target (low-density lipoprotein cholesterol <100 mg/dl) could add the alternative treatment on top of randomized treatment for another 12 months: 100 patients who are dyslipidemic with ischemic heart disease treated with percutaneous coronary intervention were enrolled (ezetimibe n = 50, nutraceutical n = 50). Efficacy (lipid profile) and tolerability (adverse events, transaminases, and creatine kinase) were assessed after 3 and 12 months. After 3 months, 14 patients in the nutraceutical group achieved their therapeutic target, whereas none of the patients in the ezetimibe group did. At 1-year follow-up, 58 patients (72%) of the combined therapy group and 14 (100%) of the nutraceutical group reached the therapeutic goal. No patients experienced important undesirable effects. In conclusion, nutraceuticals alone or in combination with ezetimibe are well tolerated and improve the lipid profile in statin-intolerant patients with coronary heart disease. Further studies are needed to assess long-term effects of nutraceuticals on mortality.

Lipids Health Dis. 2012. Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern in hypercholesterolemic subjects and its additive effect in patients with familial hypercholesterolemia on stable cholesterol-lowering treatment. Although statins (STs) are drugs of first choice in hypercholesterolemic patients, especially in those at high cardiovascular risk, some of them are intolerant to STs or refuse treatment with these drugs. In view of this, we have evaluated the lipid-lowering effect of a nutraceutical pill containing berberine (BBR) and of ezetimibe, as alternative treatments, in monotherapy or in combination, in 228 subjects with primary hypercholesterolemia (HCH), with history of STs intolerance or refusing STs treatment. In addition, since PCSK9 was found up-regulated by STs dampening their effect through an LDL receptors (LDLRs) degradation, and BBR suppressed PCSK9 expression in cellular studies, we supplemented the stable lipid-lowering therapy of 30 genotype-confirmed Familial Hypercholesterolemia heterozygotes (HeFH) with BBR, searching for a further plasma cholesterol reduction. Plasma lipid pattern was evaluated at baseline and during treatments. In HCH subjects the nutraceutical pill resulted more effective than EZE in lowering LDL cholesterol and better tolerated. On treatment, LDL-C level below 3.36 mmol/L (≤130 mg/dl) was observed in 28% of subjects treated with the nutraceutical pill and 11% of those treated with EZE. In the group treated with EZE the subjects carrying the G allele of the g.1679 C > G silent polymorphism of NPC1L1 gene showed a higher response to EZE than homozygous for the common allele. Combined treatment with these drugs was as effective as STs in moderate doses (LDL cholesterol -37%, triglycerides -23%). In HeFH patients the addition of BBR resulted in LDL cholesterol reductions inversely related to those induced by the stable therapy, with mean 10.5% further decrease. The alternative treatments tested in our HCH subjects were rather effective and safe. The findings in HeFH patients suggest that berberine might act in vivo increasing expression and stability of LDLRs and/or suppressing PCSK9 expression.

Acta Diabetol. 2011. Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption. Plant sterols lower serum cholesterol concentration. Available data have confirmed the lipid-lowering efficacy in adults, while there is a relative dearth of data in children and almost exclusively restricted to subjects with familial hypercholesterolemia (FH). Aim of the present study was to evaluate the efficacy, tolerability and safety of plant sterol supplementation in children with different forms of primary hyperlipidemias. The effect of plant sterol consumption on plasma lipids was evaluated in 32 children with heterozygous FH, 13 children with Familial Combined Hyperlipidemia (FCH) and 13 children with Undefined Hypercholesterolemia (UH) in a 12-week open-label intervention study using plant sterol-enriched yoghurt. Plasma lipids and apolipoproteins were measured by routine methods. Markers of cholesterol synthesis (lathosterol) and absorption (campesterol and sitosterol) were measured by GC-MS. Tolerability and adherence to recommended regimen was very high. A significant reduction was observed in LDL-cholesterol in the three groups. Lathosterol concentrations were unchanged, reflecting a lack of increased synthesis of cholesterol. Of the two absorption markers, only sitosterol showed a slight but significant increase. Daily consumption of plant sterol dairy products favorably changes lipid profile by reducing LDL-cholesterol. To our knowledge, this is the first report of the use of plant sterols-enriched foods in treating children with primary hyperlipidemia such as FCH and UH, likely to be the most frequent form also in the young age in the western populations.

Nutr Metab Cardiovasc Dis. 2011. The treatment of hypercholesterolemic children: efficacy and safety of a combination of red yeast rice extract and policosanols. The prevention of cardiovascular risk, as occurs in lipoprotein disorders, is required since childhood. Aim of the study was to evaluate, in a group of children affected by primary dyslipidemia, the efficacy, tolerability and safety of a short-term treatment with a dietary supplement containing red yeast rice extract and policosanols. 40 children affected by heterozygous Familial Hypercholesterolemia (FH) (n=24) and Familial Combined Hyperlipidemia (FCH) (n=16), aged 8-16 years, were enrolled in a double-blind, randomized, placebo-controlled, cross-over trial. After a 4-week run-in period with only dietary advice, children received a dietary supplement containing 200mg red yeast rice extract, corresponding to 3mg of monacolins, and 10mg policosanols once-daily and placebo for 8 weeks, separated by a 4-week washout period. Lipid profile was assessed after each treatment period. The dietary supplement, compared with the placebo, significantly reduced total cholesterol by 18%, LDL-C levels by 25%, and apolipoprotein B by 25% when patients were considered as a whole group. Similar results were obtained when FH and FCH were considered separately and no significant difference between groups was detected. No significant differences were observed in HDL-C and apolipoprotein A-I levels. No adverse effects were detected when liver and muscular enzymes (AST, ALT, and CK) were determined. The treatment with a dietary supplement containing red yeast rice extract and policosanols has been for the first time successfully employed in hypercholesterolemic children. Results indicate this strategy as an effective, safe and well tolerated in a short-term trial.

Role for garlic or onions as alternatives?
Since garlic and onions have positive effects on nitric oxide, I wonder if they would be of benefit.

J Intern Med. 2015. Arginase inhibition improves endothelial function in patients with familial hypercholesterolaemia irrespective of their cholesterol levels. Elevated LDL cholesterol is an important risk factor for atherosclerosis. Endothelial dysfunction, an early event in the development of atherosclerosis, is characterized by a reduction in nitric oxide (NO) bioavailability. Arginase has emerged as a key regulator of endothelial function through competition with NO synthase for the common substrate l-arginine. Arginase in endothelial cells is activated by oxidized LDL. The study aim was to investigate the importance of arginase for endothelial dysfunction in patients with familial hypercholesterolaemia (FH). Endothelial function was evaluated in 12 patients with heterozygous FH and 12 age-matched healthy normocholesterolaemic subjects using forearm venous occlusion plethysmography. The evaluations in FH patients occurred when they were on lipid-lowering therapy and 4 weeks after withdrawal of treatment. In FH patients LDL cholesterol increased. Arginase inhibition enhanced EDV in FH patients by a similar degree independent of lipid-lowering therapy. The improvement in EDV by arginase inhibition was significantly greater in FH patients than in the control group. Arginase inhibition results in greater improvement in endothelial function in patients with FH compared to healthy controls irrespective of their cholesterol levels. Arginase may be a promising therapeutic target for improving endothelial function in patients with hypercholesterolaemia.

Statin drug therapy benefits versus harm or side effects
I will list some of the harm or danger of statin therapy followed by some of the benefits.

Diabetes, increased blood sugar
Drug Saf. 2016. Long-Term Outcomes of Short-Term Statin Use in Healthy Adults: A Retrospective Cohort Study. ata suggest that the beneficial cardiovascular effects of statins are maximized after the first year of statin use; yet, the timeline of statin-associated adverse events is not well delineated. To examine the associations of short-term statin use (≤1 year) with short- and long-term adverse events and beneficial cardiovascular outcomes in a 'healthy' cohort. A cohort study of a healthy Tricare population (fiscal year [FY] 2002 through FY 2011) who have no cardiovascular disease, major comorbidities requiring medications, or functional limitations. Statin users used statins for 90-365 days during FY 2005 as their only prescription medication. Nonusers had medical encounters but did not receive prescription medications during FY 2005, and did not receive any statins throughout the study period from FY 2002 to FY 2011. Outcomes were the occurrence of major acute cardiovascular events, diabetes mellitus and its complications, kidney diseases, musculoskeletal diseases, obesity, cataracts, malignancy, and death. We matched 1525 statin users to 1525 nonusers. During the follow-up period (FY 2006 to FY 2011), statin users had significantly higher odds of developing diabetes and diabetic complications that persisted throughout follow-up. Short-term statin use was not associated with decreased odds of major acute cardiovascular events. There were no differences in risks of kidney diseases, musculoskeletal diseases, or malignancy. Short-term statin use for primary prevention in this healthy cohort was associated with an increased risk of long-term diabetes and diabetic complications without cardiovascular benefits. Further study using pragmatic studies and prospective observational studies appropriately equipped to eliminate unidentified confounders are urgently needed.

Glaucoma
Medicine (Baltimore). 2015. Association Between Statin Use and Open-angle Glaucoma in Hyperlipidemia Patients: A Taiwanese Population-based Case-control Study. The aim of the study was to investigate the association between statin use and open-angle glaucoma (OAG) risk in hyperlipidemia patients.. Clinicians should be cautious of hyperlipidemia patients with a high dosage of statin use because it might be associated with an increased risk of OAG.

Heart attack survivors placed on statin therapy, no benefit?
PLoS One. 2015. Effects of Statin Therapy on Clinical Outcomes of Survivors of Acute Myocardial Infarction with Severe Systolic Heart Failure. Large randomized trials have failed to show a beneficial effect of statin treatment in chronic HF. The investigators tried to evaluate the long-term effects of statin therapy in patients with new onset heart failure (HF) following acute myocardial infarction (AMI). Between January 2008 and December 2011, a total of 13,616 AMI patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) which was a prospective, multi-center, nationwide, web-based database of AMI in Korea. From this database, we studied 1,055 patients with AMI who had newly developed severe acute HF [left ventricular ejection fraction ≤ 40%] and were discharged alive. The patients were divided into two groups, a statin group (n = 756) and a no-statin group (n = 299). We investigated the one-year major adverse cardiovascular events (MACEs), including all-cause mortality, MI, and any revascularization of each group. We then performed a propensity-score matched analysis.RESULTS:In the original cohort, one-year MACEs were similar between the two groups (16.5% vs. 14.7% in the statin or no-statin groups; p = 0.47). Propensity-score matching yielded 256 pairs, and in that population we observed comparable results in terms of MACEs (18.0% vs. 12.5% in the statin or no-statin groups, p = 0.11) and mortality (5.1% vs. 3.5% in the statin or no-statin groups, p = 0.51). Cox-regression analysis revealed that statin therapy was not an independent predictor for occurrence of a MACE or all-cause mortality. Statin therapy was not associated with a reduction in the long-term occurrence of MACEs or mortality in survivors of AMI with severe acute HF in this retrospective cohort study.

Curr Opin Lipidol. 2015. Cardiac computed tomography imaging in familial hypercholesterolaemia: implications for therapy and clinical trials. The purpose of the present review is to summarize the potential clinical applications of computed tomographic angiography (CTA) in familial hypercholesterolemia so far and recent advances of CTA research in other high-risk patients. Long-term, aggressively statin-treated, asymptomatic familial hypercholesterolemia patients may still have dramatic coronary artery disease (CAD).  CTA imaging has made clear that an increased plaque burden can be present even among asymptomatic, long-term aggressively statin-treated familial hypercholesterolemia patients. In the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry, nonobstructive CAD predicted all-cause mortality and statin treatment improved the life span of persons with nonobstructive CAD. Clinical trials with CTA are required to develop and test identification of CAD and personalized treatment strategies for familial hypercholesterolemia.

Longevity, lifespan
Do statins help people live longer if they have familial hypercholesterolemia?
   A. Good question. As of 2016 I do not know the answer to whether those with familial hypercholesterolemia, when started therapy with statins in their 20s, 30s, or 40s live longer if they are medicated with these drugs. Perhaps their risk for heart disease and stroke is lessened, but they could die prematurely from various other side effects of statin medications. I am just guessing at this point. Or, they may live longer but their quality of life may be reduced.

Muscle damage
Endocrinol Nutr. 2016. Statin-related myotoxicity. Statin therapy has a very important role in decreasing cardiovascular risk, and treatment non-compliance may therefore be a concern in high cardiovascular risk patients. Myotoxicity is a frequent side effect of statin therapy and one of the main causes of statin discontinuation, which limits effective treatment of patients at risk of or with cardiovascular disease. Because of the high proportion of patients on statin treatment and the frequency of statin-related myotoxicity, this is a subject of concern in clinical practice.

Statin therapy benefits
Cardiol Clin. 2015. Familial hypercholesterolemia. FH is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen, and low-density lipoprotein (LDL) apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with familial hypercholesterolemia.

Curr Cardiol Rep. 2015. New Approaches in Detection and Treatment of Familial Hypercholesterolemia. Statins are the first-line therapy of choice for FH patients as they have been proven to reduce CVD risk across a range of conditions including hypercholesterolemia (though not specifically tested in FH).

Curr Opin Lipidol. 2015. Early initiation of statin treatment in children with familial hypercholesterolaemia. This article provides recent insights on the early onset of atherosclerosis in heterozygous familial hypercholesterolemia and reports on novel treatment options as well as on the consequences of long-term statin use in childhood. Children with familial hypercholesterolemia have greater mean carotid intima-media thickness (cIMT) than their unaffected siblings even before the age of 8 years, which is several years earlier than previously reported. In those children, 2 years of rosuvastatin treatment resulted in slowing of the cIMT progression. In addition, in a 10-year follow-up study after a pravastatin intervention trial, long-term statin therapy in young adult familial hypercholesterolemia patients was associated with normalization of cIMT progression and appeared effective in prevention of very premature cardiovascular events. These effects were observed without untoward safety concerns. However, a majority of these young adults did not reach cholesterol goals according to general guidelines, indicating the need for improvement of treatment in this patient group. The importance, efficacy and safety of early initiation statin therapy in familial hypercholesterolemia children were further confirmed by recent findings. Nevertheless, to reach current treatment goals, the use of more potent statins is required and has been proven well tolerated and effective in young children.

Stroke risk reduction
Atherosclerosis. 2015. Statins decrease the risk of stroke in individuals with heterozygous familial hypercholesterolemia: A systematic review and meta-analysis. Familial hypercholesterolemia (FH) is undoubtedly associated with premature coronary heart disease, but it is debatable whether FH increases the risk for stroke. To meta-analyze available evidence regarding the incidence of stroke in individuals with heterozygous (He) FH. We conducted a systematic review and a meta-analysis of epidemiological studies, including English-language publications until June 2015; four observational studies, with 3374 participants with HeFH, were included in the analysis. Cerebrovascular disease comprised of ischemic stroke or transient ischemic attack. Since studies did not include any control subjects, the corresponding general population of the same reference area and period of time for each HeFH study served as control group. Analyses were performed according to the period of time during which the studies were conducted: prestatin and statin era (before and after 1987 when lovastatin was launched). In the prestatin era, individuals with HeFH exhibited a higher risk for stroke compared with the general population. In contrast, FH subjects had a lower odds for stroke following the generalization of statin therapy. Taking into account the small number of studies and methodological issues, HeFH was associated with a higher risk of cerebrovascular disease compared with the general population in the prestatin era, which was significantly reduced after the introduction of statin therapy.

Angiology. 2015. Statin Therapy May not Effect NLR and MPV Levels in Patients With Hypercholesterolemia: A Retrospective Study. Statins may exert pleiotropic effects in coronary artery disease (CAD), diabetes mellitus, and familial hypercholesterolemia. We evaluated the effects of statins on the neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV) in 261 consecutive patients with hypercholesterolemia having CAD or at high cardiovascular (CV) risk and 50 healthy participants who were retrospectively included in this study. Patients were treated with 10 to 80 mg atorvastatin or 10 to 40 mg rosuvastatin for 24 weeks according to baseline levels of cholesterol, triglycerides, and CV risk. Baseline NLR and MPV were significantly higher in patients with CAD or at high risk compared to the control group. The NLR, MPV, and lipid parameters were also compared in the patient group after statin treatment for 24 weeks. Lipid levels decreased but the NLR and MPV did not change significantly after the statin therapy. Further studies are needed to clarify the effect of statin therapy on NLR and MPV in patients with CAD or at high CV risk.

Discontinuing treatment
Intern Med J. 2016. Discontinuation of statins in a population of older New Zealanders with limited life expectancy. Discontinuation of statins may be considered for older individuals with a cancer, multi-morbidity, approaching end-of-life and in primary prevention. The aim of this study is to investigate the relationship between the rates of statin discontinuation in the last 12 months of life and a diagnosis of cancer, and in individuals using statins for primary or secondary prevention. A case-control study of matched cases and controls. Matching was based on age, Charlson comorbidity index scores and socioeconomic status. Prescription and diagnostic data for 20 482 individuals who were aged over 75 years, were in their last 12 months of life and were receiving statins during the study period. After propensity score matching, we identified 4832 cases with a diagnosis of cancer and 4809 matched controls. We used Cox regression to test the relationship between the relative risk of statin discontinuation and a diagnosis of cancer, and in individuals using statins for primary or secondary prevention. Statins were discontinued in 70% of older adults with a diagnosis of cancer and 55% of those without cancer. The Cox regression analysis supports that a diagnosis of cancer can increase the rate of statin discontinuation compared with individuals without a diagnosis of cancer regardless of whether statins were used for primary or secondary prevention. The findings from this study support that statins are likely to be discontinued in the last year of life in older people with limited life expectancy from cancer, even if statins were indicated for secondary prevention of cardiovascular disease.