Inositol and Cholesterol

What is Inositol?

Inositol is a carbohydrate that was once considered a B vitamin. However, it is not an essential nutrient because it is synthesized from glucose in the required amount in the body.

While there are nine forms (stereoisomers) of inositol, the most important of the natural isomers is the myo form.

Inositol is also found in certain plants. Fruits such as oranges and cantaloupe contain inositol and its phosphates while seeds, nuts, beans, and high-bran cereals contain inositol hexaphosphate also known as phytates.

However, phytates are not digestible and, therefore, they are not good sources of inositol. On the other hand, lecithin (another plant component rich in inositol) are easily digested and well-absorbed. Therefore, they provide a ready plant source of inositol.

Health Benefits of Inositol

The best clinical evidence supporting inositol supplementation is in the treatment of psychiatric disorders. Myo-inositol is effective in the treatment of depression, obsessive-compulsive disorder, panic disorder, agoraphobia, and bulimia.

Besides psychiatric disorders, inositol has also shown great promise in the treatment of insulin resistance and polycystic ovarian syndrome.

A few studies investigating the benefits of inositol in the treatment of metabolic syndrome in postmenopausal women showed that inositol can lower serum triglycerides levels and increase the level of high-density lipoprotein (HDL or “good”) cholesterol.

Inositol, Flush-Free Niacin, and Cholesterol

Inositol As A Lipotropic Agent

Although a few studies indicate that inositol can lower blood cholesterol, most of these studies did not directly investigate the cholesterol-lowering benefits of inositol.

Studies that directly investigated inositol as a lipid-lowering agent found some evidence to support any recommendation for inositol in the treatment of hyperlipidemia. However, there is strong evidence that inositol has a lipotropic effect.

As a lipotropic agent, inositol prevents cholesterol from accumulating in the liver, and therefore, reduces the risk of developing fatty liver.

This effect is important to the lipid metabolism in the body because the liver is an important organ for cholesterol synthesis, metabolism, and excretion.

However, it is very likely that the lipotropic effect of inositol only has a small effect on cholesterol levels.

As a lipotropic agent, inositol promotes the redistribution of body fat especially away from the liver. Because it keeps fat from solidifying by emulsifying it, it can prevent the clogging of the arteries and the thickening of their walls.

Therefore, inositol may have other cardiovascular benefits besides its effect on cholesterol levels.

In fact, inositol supplements are rarely used to lower cholesterol. Instead, a complex of niacin and inositol is actively marketed as a cholesterol-lowering supplement.

Enter Niacin

Niacin or vitamin B3 is an essential nutrient and one of the 5 vitamins associated with serious deficiency syndromes (the others are thiamin or vitamin B1, vitamins A, C, and D).

Niacin has a proven and potent cholesterol-lowering effect. It works by inhibiting the breakdown of fat in the adipose tissue. By preventing the release of lipids from the adipose tissue, niacin lowers the amount of VLDL (very low-density lipoprotein) cholesterol synthesized in the liver.

Since LDL (low-density lipoprotein or “bad”) cholesterol is made from VLDL, niacin lowers the levels of free fatty acids in the blood.

In addition, this vitamin increases the blood level of HDL (high-density lipoprotein or “good”) cholesterol.

These changes to blood cholesterol levels improve the body’s lipid profile and reduce the risks of cardiovascular diseases.

Nicotinamide and nicotinic acid are the two common vitamin B3 supplements on the market. Nicotinamide does not lower blood cholesterol nor does it improve the lipid profile.

Although nicotinic acid is very effective for lowering blood cholesterol, it causes some nasty side effects such as itching, flushing and hot flashes. To reduce these side effects, a third niacin supplement is commonly recommended. This supplement is known as no-flush or flush-free niacin.

No-Flush Niacin

No-flush niacin is also known as inositol hexaniacinate. It is made from nicotinic acid and inositol.

No-flush niacin is formulated from the combination of six molecules of nicotinic acid and one molecule of inositol. This special niacin formulation acts as a vasodilator and it is also meant to slowly release nicotinic acid. Therefore, it opens up the blood vessels to improve blood flow and avoid the spike in the blood niacin level as well as the “flushing” that accompanies the spike.

Unfortunately, there is very little evidence to support the use of flush-free niacin in lowering blood cholesterol.

In fact, there are more studies indicating that this combination of niacin and inositol does not affect the levels of total cholesterol, triglycerides, LDL cholesterol or HDL cholesterol than there are studies to show flush-free niacin improves lipid profile.

Therefore, while a few studies found that inositol hexaniacinate can slightly or considerably lower cholesterol levels when compared to standard niacin supplements, most studies found that the inositol-niacin complex was ineffective.

In one study, a group of researchers demonstrated that inositol hexaniacinate did not release its niacin molecules readily and, therefore, produced far less blood nicotinic acid level than a standard niacin supplement.

Overall, experts agree that there is currently not enough studies to judge the cholesterol-lowering benefits of inositol hexaniacinate.

Studies on Inositol and Cholesterol

Can Inositol Lower Cholesterol?

Inositol as a lipid-lowering agent has been studied for a long time. One of the earliest studies was published in the journal, Experimental Biology and Medicine, in 1949.

In that study, the researchers confirmed that inositol can indeed lower serum cholesterol and lipoprotein levels. They called for more studies to determine how inositol affects lipid levels and how it can be used in the treatment of hyperlipidemia.

The cholesterol-lowering effect of inositol has also been confirmed in recent studies.

In a study published in 1999 in the journal, Anticancer Research, researchers from the California Institute of Medical Research investigated the anti-cancer and lipid-lowering effects of inositol hexaphosphate.

Inositol hexaphosphate is one of the phosphate salts of inositol commonly found in food plants.

In the part of this study dedicated to determining the effects of inositol on blood lipid levels, the researchers gave the inositol compound to a group of Fischer rats fed on either cholesterol-rich or standard diet.

The results of the study showed that inositol significantly lowered the raised serum total cholesterol and triglyceride levels in the rats fed a cholesterol-rich diet. Inositol also reduced serum lipid levels in the rats fed on a standard diet.

The researchers concluded that inositol hexaphosphate qualified as a potential therapeutic agent in the treatment of hyperlipidemia.

In Postmenopausal Women with Metabolic Syndrome

The best clinical evidence for the lipid-lowering property of inositol comes from a set of studies investigating the benefits of myo-inositol supplementation for postmenopausal women suffering from metabolic syndrome.

The first study was published in 2011 in Menopause: The Journal of North American Menopause Society.

The researchers investigated the insulin-sensitizing benefits of myo-inositol for alleviating some of the symptoms of metabolic syndrome.

For this study, they recruited 80 postmenopausal women suffering from metabolic syndrome. These women were divided into 2 groups. One group received 2 g of myo-inositol two times daily for 6 months while the other group got a placebo for the same duration.

The study results showed that myo-inositol

• Reduced diastolic blood pressure by 11%
• Reduced insulin resistance by 75%
• Reduced serum triglycerides by 20%
• Increased HDL cholesterol by 22%

The researchers concluded that myo-inositol can be used to improve the symptoms of metabolic syndrome in postmenopausal women.

Clearly, inositol can improve the lipid profile by lowering the triglyceride level and raising the level of HDL cholesterol.

The results of the continuation of the above study were published in Climacteric: The Journal of the International Menopause Society in 2012.

Using the same study design, the same dose of myo-inositol and placebo but continuing the study for another 6 months, the researchers showed that long-term inositol supplementation was not only safe but also reduced blood pressure and insulin resistance as well as lowered the levels total cholesterol and serum triglycerides while increasing HDL cholesterol level.

The researchers concluded with the same recommendations as the previous study but with stronger emphasis and more confidence in the cholesterol-lowering benefits of inositol.

Inositol + Red Yeast Rice Statin

An Italian study published in the journal, Minerva Ginelogica, in 2013 extended the last two studies by comparing the lipid-lowering benefits of inositol to inositol plus monacolin K.

Monacolin K is a natural compound and statin extracted from red yeast rice. It is a proven cholesterol-lowering agent and is actually the same as lovastatin, the popular cholesterol-lowering drug.

The researchers divided a number of women suffering from polycystic ovarian syndrome into 2 groups. The first group received myo-inositol while the second group received myo-inositol plus monacolin K.

The results of the study showed that both treatments reduced blood cholesterol levels and improved insulin sensitivity. However, the combination of inositol and monacolin K provides better lipid-lowering results.

Wax-matrix Extended-Release Niacin vs. Inositol Hexanicotinate

A 2013 study published in the Journal of Clinical Lipidology compared the lipid-lowering effects of “flush-free” niacin to a new niacin formulation known as wax-matrix extended-release niacin.

Both niacin formulations are designed to slowly release niacin and, therefore, reduce the severity of undesirable side effects such as itching and flushing.

The researchers first placed the participants (120 people with mild to moderate dyslipidemia) on a specific diet for 4 weeks before dividing them into 3 groups of 40 participants each. While one group was given a placebo, the other two groups received either 1500 mg/day of inositol hexanicotinate or the same dose of wax-matrix extended-release niacin for 6 weeks.

The study results showed that there was no significant improvement in lipid levels in the groups receiving placebo or inositol hexanicotinate.

However, the group receiving wax-matrix extended-release niacin experienced an 11% reduction in total cholesterol level, an 18% reduction in LDL cholesterol level, a 15% reduction in non-HDL cholesterol level and a 12% increase in HDL cholesterol level.

The researchers also discovered the reason for the sharp differences between the two niacin groups. They found that very little niacin was released from inositol hexanicotinate compared to the slow but steady release of niacin from the wax-matrix supplement over 6 hours.

This study showed that inositol hexanicotinate should be avoided as a cholesterol-lowering agent even though both its constituents (inositol and niacin) have been proven to lower cholesterol and improve lipid profile.

In all likelihood, the bound between niacin and inositol may be too strong to be easily broken by digestive enzymes. Such a strong bond would inhibit the absorption of the compound and the release of its constituents.