Metabolic
Syndrome and Cardiovascular Disease
Cardiovascular disease (CVD) is a major cause
of mortality worldwide, responsible for 17.3 million deaths each year.
Metabolic syndrome refers to the “perfect storm” of high blood pressure, high
cholesterol, abnormal blood sugar regulation, and the presence of
intra-abdominal fat accumulation. This cluster of disorders affects about
30-40% of Americans and increases the risk of developing CVD and Type 2
diabetes.
Dietary and lifestyle changes are obvious and
effective measures of prevention and treatment, however, many individuals find
these types of changes too difficult. Other times individuals may need extra
support if areas such as blood pressure, blood sugar or cholesterol aren’t
coming into normal range within a reasonable amount of time.
Conventional treatments utilize medications
such as diuretics and beta blockers to control blood pressure, and statins to
control cholesterol levels. These medications, however, can cause side effects
that dissuade patients from starting or continuing treatment. Food-related
supplementation offers a treatment option with fewer side effects and, in many
cases, equal clinical outcomes.
Managing
Cholesterol: Statin Medications vs. Red Yeast Rice Extract
Statins are a group of pharmaceutical drugs
designed to block the enzyme HMG-CoA reductase which prevents the production of
cholesterol in the liver.
Although effective in lower cholesterol, the
side effects of statins are often significant enough to dissuade patients from
starting or continuing treatment. These include muscle pain and weakness,
fatigue, worsening of blood sugar control and diabetic status, and increases in
liver enzymes (typically a marker for liver cell damage). It has been reported
that about 10-15% of patients taking statins will experience muscle-related
side effects alone.
Red yeast rice (RYR) consists of a specific
species of yeast called Monascus
purpureus which is cultured on rice. The result of this cultivation is the
production of a mixture of compounds called monacolins which act like statin
medications by inhibiting the same HMG-CoA reductase enzyme. Monocolin K,
specifically, is identical to the drug known as lovastatin, but with higher
bioavailability in RYR extracts, compared to prescribed amounts of the
medication.
Many studies have shown that just 10 mg
of monocolin K from RYR can maintain normal LDL cholesterol levels. As well, a 2014 meta-analysis that gathered data from 13 randomized,
placebo-controlled trials with a total of 804 patients, showed that RYR was
able to significantly decrease serum total cholesterol (TC), triglycerides, and
LDL cholesterol compared to placebo.
One study compared RYR treatment (1200 mg
daily) with the statin drug simvastatin (20 mg daily) to assess differences in
reported side effects over four weeks. The result of treatment in both groups
led to similar reductions in TC and LDL cholesterol, however, the group given
simvastatin had significantly increased fatigue scores from baseline, and
significantly greater fatigue scores than the RYR group.
Food-related
Treatments: Olive and Fish Oil with Red Yeast Rice
Many studies have looked at combinations of
food supplements for the benefit of multiple components associated with
metabolic disease. One example of this is olive oil: polyphenols from olive
extracts have enough antioxidant action to protect LDL particles from oxidative
damage. Why is this so important? Oxidation of LDL cholesterol particles is a
driving factor in atherosclerosis and increases the risk of CVD.
In fact, most CVD-related deaths are the
result of atherosclerosis: a narrowing of the arteries due to the formation and
deposition of lipid-based plaque. When these plaques rupture or are dislodged,
they are set loose in the circulation, but can act like a plug (called a
thrombus) within narrower arteries. When a thrombus gets stuck and blocks blood
flow this can cause a heart attack or stroke.
The development of atherosclerosis isn’t only
dependent on lipids and cholesterol, but on inflammation and specific immune
cells involved in inflammation. Oxidized LDL (oxLDL) has been identified as the
promoting factor in this inflammatory response in atherosclerosis.
Getting into the science of it, when there are
circulating particles of oxLDL, they promote the binding of these immune cells,
called monocytes, to the endothelial cells of blood vessels. Once there,
there’s a very high chance of them setting off the chain of events that lead to
plaque development.
This process is specific to oxLDL, but not
necessarily LDL on its own. Therefore when we treat or try to prevent CVDs,
it’s important to address LDL cholesterol levels, but also oxidative stress,
which is where using antioxidants have an important and critical role.
Olive
Polyphenols: Our Antioxidants.
Specifically, the polyphenol hydroxytyrosol
(HT) from olive extracts have shown great results in treating components of
metabolic syndrome. For example, many clinical trials have shown that olive oil
can efficiently lower blood pressure. But most notably, HT protects against the
oxidation of LDL particles.
In a
double-blind, placebo-controlled trial, 50 unmedicated patients with metabolic
syndrome were randomized to treatment with both 10 mg of monocolins from
RYR and 10 mg HT.
The result of this study was a decrease in LDL
concentration by 24% in the treatment group, and an increase by 1% in the
placebo group. But even more clinically relevant was the decrease in oxLDL in
the treatment group (-20%) compared to a 5% increase in the placebo group.
Another result found in this study was the
decrease of a particle called apoB by 6%, whereas the control group had an
increase in apoB by 6%. And blood pressure as well decreased on average by 10/7 mmHg
with RYR and HT treatment.
What
is apoB and why is this significant?
Apolipoprotein B (apoB) is a measure of the
total circulating atherogenic particles. It gives a more accurate measurement
of LDL particles than our current methods – which in actual fact are calculations – of LDL.
Apolipoproteins are proteins that help to
transport fat soluble (hydrophobic) particles in the blood, and they can bind
to cells to help deliver lipids to target organs and tissues. Specifically apoB
is associated with LDL and VLDL particles. The concentration of apoB indicates
the total number of potentially atherogenic particles and has been described as
a better predictor of atherosclerosis than LDL concentrations themselves.
What
about when my doctor orders a blood test for cholesterol, including LDL?
LDL levels on blood work are calculated with a
specific equation, rather than actually measuring the concentration of LDL. As
an estimation, there are potential analytical errors in this method. However,
we can measure apoB directly in the plasma (with a method not available to
LDL), making this more accurate for determining cardiovascular risk.
One component that didn’t change with these
food-related treatments was waist circumference. Unfortunately, there is no
magic weight-loss solution here which is why including dietary and lifestyle
(exercise) changes are often still required.
Magnitude
of Effect: How Much Should I Take and How Much Will It Help?
One group of researchers calculated the
fraction and absorption of HT in olive oil and concluded that individuals in
Mediterranean countries consume approximately 30-50 g of olive oil daily,
resulting in the absorption of 4-9 mg of olive oil phenols. Considering that
the above study used between 9 and 10 mg of HT daily, it’s possible to obtain a
similar amount from the diet, assuming a Mediterranean-style diet.
Another study tested the effects of combining
5 mg of monocolin K with an omega-3 fatty acid supplement (equivalent to about 610 mg daily) in a
similar phytosterol approach to treating metabolic syndrome.
The results were a significant decrease in TC
(-16%) and LDL (-22%). These researchers estimated, based on current knowledge
that a decrease of this magnitude is associated with a reduction by 20% in
cardiovascular disease events over the following 10 years.
There’s no question how devastating CVD can be
and the risk it imposes, especially heart attacks and strokes. However, our
knowledge base on how these diseases progress and the tools that we have to
prevent and treat them are expanding. Individuals with metabolic syndrome (or
even one more of its components) have both pharmaceutical and food-based
treatment options that can be equally beneficial. Even more so, food-based
options such as RYR may save individuals from experiencing harsh side effects
that could deter them from treatment.
References
- Cicero AFG, Derosa G, Pisciotta L, Barbagallo C. Testing the short-term efficacy of a lipid-lowering nutraceutical in the setting of clinical practice: a multicenter study. J Med Food. 2015; 18(11): 1270-73
- Li Y, Jiang L, Jia Z, Xin W, Yang S, Yang Q, Wang L. A meta-analysis of red yeast rice: an effective and relatively safe alternative approach for dyslipidemia. PLoS One. 2014; 9(6): e98611
- Lima LM, Carvalho Md, Sousa MO. Apo B/apoA-I ratio and cardiovascular risk prediction. Arg Bras Cardiol. 2007; 88(6): e187-90
- Peyrol J, Riva C, Amiot MJ. Hydroxytyrosol in the prevention of the metabolic syndrome and related disorders. Nutrients. 2017; 9(3): pii:E306
- Rhoads JP, Major AS. How oxidized low-density lipoprotein activates inflammatory responses. Crit Rev Immune. 2018; 38(4): 333-42
- Verhoeven, V, Van der Auwera A, Van Gaal L, Remmen R, Apers S, Stalpaert M, Wens J, Hermans N. Can red yeast rice and olive extract improve lipid profile and cardiovascular risk in metabolic syndrome?: A double blind, placebo controlled randomized trial. BMC Complement Altern Med. 2015; 15: 52
- Xue T, Tao L, Wu S, Wang G, Qian L, Li J, Liao L, Tang J, Ji K. Red yeast rice induces less muscle fatigue symptom than simvastatin in dyslipidemic patients: a single center randomized pilot trial. BMC Cardiovasc Disord. 2017; 17(1): 127