Inositol (Inositol hexaniacinate) is a variation – considered an ‘unofficial’ member of the vitamin B family. It is also known as a supplement niacin/inositol niacinate (a.k.a. vitamin B3 or nicotinic acid and as vitamin B8), available in supplemental form. In the US and other countries around the world, several different forms of ‘niacin’ are marketed as dietary supplements:
- Nicotinic acid – immediate release and unmodified
- Inositol hexanicotinate (IHN), which doesn’t cause the typical ‘niacin flush’
It has not been associated or linked with typical toxicity caused by niacin in scientific research, so its use is prevalent for individuals who need large amounts of niacin.
Inositol nicotinate (IHN) has been likened to a “cousin” of nicotinic acid that has been known to be as effective in optimizing blood lipid levels as niacin, but without one of its most annoying side effects – flushing. It has been used in Europe for decades in the treatment of peripheral circulation issues such as intermittent claudication as well as Raynaud’s syndrome.
Nicotinate from inositol hexanicotinate is a bioavailable source of niacin, according to the European Food Safety Authority Scientific Panel on Food Additives and Nutrient Sources Added to Food in 2009 (1).
Some of these studies date back to the 1980s and include:
- Quantitative thermal imaging to assess inositol nicotinate treatment for Raynaud’s syndrome (Ring EFJ, Porto LO, Bacon PA.J Int Med Res. 1981;9:393-400)
- The therapeutic efficacy of inositol hexanicotinate (Hexopal®) in intermittent claudication: a controlled trial (O’Hara J, Jolly PN, Nicol CG. Br J Clin Pract. 1988;42:337-383)
- The effect of inositol hexanicotinate (Hexopal) in patients with Raynaud’s syndrome (Cli Trials J. 1985;22:521-529)
- Does inositol hexanicotinate (Hexopal) influence intermittent claudication? (Kiff RS. Br J Clin Pract. 1988;42:141-145)
Claudication is defined as a painful cramp in the calf caused by decreased oxygen supply to the calf muscle.
Raynaud’s syndrome or phenomenon is defined as a painful response in the hands and feet to exposure to cold, caused by the construction of blood vessels supplying the hands or the feet. It has been noted that Inositol hexanicotinate may provide more beneficial results than the use of niacin due to its enhanced tolerance and safety.
Inositol may be more familiar to consumers as nicotinic acid, or even niacin or vitamin B3. Vitamin B3/niacin is converted from tryptophan by the body. Niacin functions as a component of a number of enzymes, including nicotinamide adenine dinucleotide (NAD) and malate dehydrogenase (NADP+) (2), (3). Just these two coenzymes alone are involved in over 50 different chemical reactions in the body. Enzymes containing niacin are also important in the production of energy, metabolism of fats, cholesterol, and carbohydrates, and in manufacturing numerous body compounds, including adrenal hormone secretions, and sex hormone development and secretions.
Because niacin in its pure form may contribute to a number of side effects, supplements such as inositol hexanicotinate or HexaNiacin have become more popular. They’ve been used for over three decades in Europe with good safety records, and are also becoming more prevalent in the United States and Canada.
Important Things To Know About Inositol
Vitamin B3 is available in a variety of nutritional supplements, more commonly known as niacin, nicotinic acid or nicotinate. Vitamin B3 comes in two basic forms: niacin (a.k.a. nicotinic acid), and niacinamide (a.k.a. nicotinamide). Each of these different forms can be used for different applications for health and wellness.
Nicotinic acid (vitamin B3), in addition to its ability to process the release of energy from carbohydrates, is required to form fat from carbohydrates. It’s also necessary for the processing of alcohol.
The niacin form of the B3 vitamin takes part in the regulation of cholesterol. Niacinamide does not.
Excess vitamin B3 (inositol) is water soluble in the body, and will be excreted in urine.
Inositol is not “officially” classified or recognized as a vitamin because it is synthesized from glucose in the body, mainly by intestinal bacteria.
Inositol is found in small amounts in most body tissues, with the highest concentrations of the component in the brain, the heart, and in the eye (lens).
Myo-Inositol is one of the most common and natural forms of the supplement.
Inositol is also known as:
- Vitamin B8
- 1,2,3,4,5,6- Cyxlohexanehexol
Inositol is found in a variety of animal and plant life components. It is also manufactured in supplement form in laboratory environments.
With regard to the chemical structure, the inositol molecule is constructed of six molecules of niacin attached to a single molecule of inositol. When the supplement enters the body, it enables a lipotropic effect similar to that of choline – meaning that it promotes the transportation of fats to the liver, vital for liver health. IHN is broken down into its component parts, thereby initiating the release of niacin into the bloodstream. After this release, it is capable of performing its anti-cholesterol effects, which improves utilization of peripheral glucose, and enhances its ability to reduce levels of glycolysis products in serum. Inositol also appears to decrease metabolism of nicotinate molecules, which contributes to two major and beneficial effects on the body:
- Prevents the flushing that typically occurs with high-dose niacin treatments
- Extends anti-cholesterol effects of niacin.
How Does Inositol Work In The Body?
Research regarding the efficiency of IHN to improve lipid profiles dates back to the early 1960s. Two of these early research groups resulted in reports of reduction in cholesterol that were more obvious than that produced by straightforward niacin treatment. A clinical study performed in Germany determined that IHN, not niacin, was capable of producing “significant” reduction of levels of free fatty acids at night time over niacin, and that IHN therapy could produce prolonged reduction in blood lipid levels.
Symptoms Of Niacin (Vitamin B3) Deficiency
Niacin deficiencies, as well as deficiencies of tryptophan, may result in one of the most common signs: pellagra. The condition affects the integumentary (skin) system, digestive system, and nervous system. It was relatively common in Italy and Spain in the 1700s. This deficiency of niacin can contribute to numerous characteristics of pellagra: dementia, dermatitis, and diarrhea.
Some of the additional signs and symptoms of niacin deficiencies include but are not limited to:
- Inadequate brain function that can contribute to confusion or dementia
- Scaly, cracked dermatitis
- Diarrhea caused by impaired manufacture and function of the mucosal lining of the gastrointestinal tract
- Alopecia, patchy baldness, or hair loss and hair-pulling (trichotillomania) (4)
- Memory loss
- Decreased levels of inositol have been noted in individuals diagnosed with nerve disorders such as diabetic neuropathy and multiple sclerosis. It is believed that inositol supplements may prove beneficial in improving nerve transmission.
Deficiencies of inositol are rare because the component can be found in a number of foods. However, it has been noted that long-term use of antibiotics can promote the body’s need for the component. Excessive coffee consumption may trigger neural tube defects, and long-term and extremely high intake of coffee can initiate deficiencies (5).
Can’t I Obtain Adequate Levels Of Niacin From Food?
Niacin can be obtained from food, but recommended dietary allowances differ for infants, children, and adults. For example, in adults, the recommended daily allowance of niacin in its pure form for males 19 to 50 years old is 19 mg a day. Women between 11 and 50 years of age are recommended an average of 15 mg a day.
Niacin is found in a number of foods. Milligram content per 3.5 ounce (100 g) serving includes but is not limited to:
- Yeast (Torula) – 44.4
- Yeast (Brewer’s) – 37.9
- Rice bran – 29.8
- Wheat bran – 21.0
- Peanuts (with skins) – 17.2 (without skins) – 15.8
- Wild rice – 6.2
- Sesame or sunflower seeds – 5.4
- Brown rice – 4.7
- Whole wheat grain – 4.4
- Whole wheat flour – 4.30
How Is Inositol Used?
Inositol has a number of beneficial effects on the body, mainly in the production of energy. It is also important in the regulation of antioxidant mechanisms, detoxification reactions in the body, as well as blood sugar levels. Inositol supplements also have a positive effect on a number of health issues, especially high cholesterol levels.
The substance has been used to treat a variety of medical issues with varying effectiveness. Some of the most common include:
- Diabetic neuropathy (diabetic nerve pain) – Inositol has been reported in small studies to improve diabetic neuropathy or nerve function caused by nerve degeneration and destruction of myelin sheets that protect the nerves.
- Panic disorders
- Mental health issues (ADHD, depression, Alzheimer’s disease, schizophrenia)
- As a hair growth supplement
- High blood pressure – may increase levels of HDL (high-density lipoprotein) or “good” cholesterol, which can help reduce or prevent build-up of plaque that contributes to arteriosclerosis (hardening/thickening of the arteries) and atherosclerosis (build-up of plaque inside arteries that may break off and block a blood vessel, leading to heart attack or stroke).
- High cholesterol levels – plays an important role in the metabolism of cholesterol and fats. Inositol may act as a mild nootropic agent that can help lower blood cholesterol and remove fat from the liver.
- Higher than normal levels of testosterone.
- PCOS (Poly Cystic Ovarian Syndrome) that can also include ovulation failure – several studies have reported an improvement in the symptoms of PCOS with Inositol.
Medical research and studies have determined that Inositol, depending on milligram strength as well as other contributing drugs (prescription or over-the-counter), may also provide some benefits in treating panic disorders, or at least in controlling the level or severity of panic disorders such as agoraphobia. A small study reported that use of inositol could be as effective as some prescription medications, but larger clinical trials are required to determine the veracity of its use for reducing or preventing panic attacks (6).
A small study determined that the oral use of inositol may help reduce some of the symptoms associated with obsessive-compulsive disorders (OCD), with noticeable results evident within six weeks of use (7).
Oral doses of inositol have shown some capability in promoting the ability to ovulate (in obese women) diagnosed with polycystic ovarian syndrome (PCOS) as well as having the ability to decrease triglyceride (a form of “bad” triglyceride) levels and blood pressure (8).
There is a lack of studies regarding its efficacy in the treatment of mental disorders such as schizophrenia, dementia conditions such as Alzheimer’s, for diabetic neuropathy, treatment of ADHD, hair growth, fat metabolism, or cancer treatments.
Some limited research has reported that the use of inositol may provide initial improvements in depression, but after approximately four weeks, the symptoms reappear, and may even grow worse. Some research has suggested that combining SSRIs or antidepressant medications with inositol may prove effective, but research in this regard has shown little efficacy.
Elevated Cholesterol And Triglyceride Levels
A number of studies have been performed regarding the effect of inositol in reducing blood lipid levels, which, in turn, reduces the risk for coronary heart disease, and for some, reduces the risks of side effects of prescription drugs or niacin. Doctors are often somewhat reluctant to prescribe niacin due to conflicting opinions regarding its efficacy versus risks.
Niacin was first noted for its ability to lower the lipid levels in the 1950s, but it is also extremely effective in lowering the overall total cholesterol levels. Niacin has the capability of decreasing LDL (low-density lipoprotein or “bad” cholesterol), triglycerides, Lp(a) glycoprotein, and fibrinogen levels, while at the same time increasing HDL (good, or high-density lipoprotein) levels.
Some scientific studies have determined that high doses (1.5 to 2 milligrams per day) are effective in positively affecting blood lipids, raising HDL (good cholesterol) levels while at the same time reducing levels of bad or LDL cholesterol as well as those of triglycerides. High doses have also been reported to increase the levels of good or HDL cholesterol by 30% or more, which has a positive impact on cardiovascular health. A later study performed in 1994 determined that nicotinic acid combined with Lovastatin and Gemfibrozil also proved effective (“Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphlipoproteinanemia.”).
Another popular and well-known study (the Coronary Drug Project) determined that niacin was one of the only lipid lowering agents that have the potential to reduce overall mortality. Fifteen years later, a follow-up study determined that long-term death rate was approximately 11% lower than the group that received a placebo, though most patients had discontinued participation in the study years earlier. (Specifics noted in the Journal of Am Coll Cardiol 8, 1245-1255, 1986).
Newer developments of statin drugs as well as Gemfibrozil have not yet determined if efficacy is as encouraging in reducing potential mortality. Studies in this area continue. This area of study is of special importance to renal transplant patients, where lipid abnormality is frequent, as well as cardiovascular disease – a primary cause of morbidity and mortality in such patients. Determining the value, safety, and efficacy of niacin as opposed to Lovastatin has been studied as well.
One such study was relatively small (12 renal transplant patients also diagnosed with persistent hyperlipidemia in spite of six weeks of dietary treatment). The trial was a randomized, prospective, and opened-labeled crossover trial following 16 weeks of therapy with 3 g niacin daily. Total cholesterol levels in these patients declined from 312 to 229 mg per deciliter. LDL cholesterol levels dropped from 218 to 142 mg per deciliter. Triglycerides dropped from 255 to 150 mg per deciliter. HDL cholesterol increased from 44 to 58 mg per deciliter.
The use of Lovastatin produced less significant results and improvements, though changes in high-density lipoprotein cholesterol or triglycerides levels were noted in the use of Lovastatin.
Treatment Of Depression
Research has determined that inositol acts as an important second messenger system in brain function. Individuals diagnosed with depression have often been noted to have a decrease of inositol in their cerebrospinal fluid.
Since the 1990s, inositol has been analyzed for its potential to possibly relieve symptoms of depression and mental anxiety. One study (relatively small with 28 patients) involved patients given 12 g daily, revealing “significant” antidepressant effects. However, the effects rapidly diminished with cessation of the supplement. A follow-up of the study and analysis of Hamilton Depression Scale scores 10 to 12 months following the study did not provide significantly different effects (9).
A number of controlled clinical trials regarding the use of inositol for potential treatment for depression, panic attacks, agoraphobia, OCD, Alzheimer’s, attention deficit disorders, and even autism have been conducted over the years. An abstract providing basic information regarding such trials, and though older (1997), shows that the interest in the use of inositol has and will continue to be studied for efficacy in a number of treatment scenarios (10).
Treatment Of PCOS
Inositol may relieve the symptoms of polycystic ovarian syndrome. According to the PCOS Nutrition Center, roughly nine forms of inositol have been created to date, with two of them showing positive results in treatment:
- D-chiro-inositol (DCI)
- Myo (MYO) inositol
The PCOS Nutrition Center states that the use of these supplements can improve a number of metabolic factors. In the US, a drug called Ovasitol combines these two. Manufactured by Theralogix, Ovasitol is marketed to:
- Enhance ovarian function and a quality
- Promote sensitivity to insulin
- Support hormone levels
This drug is specifically designed to promote normal variant function and menstrual irregularity (11). A 2012 study published in the European Review for Medical Pharmacological Science provided background that specified women diagnosed and affected by PCOS are also often diagnosed with compensatory hyperinsulinemia and insulin resistance. The study focused on whether myo-inositol and D-chiro-inositol molecules would have a synergistic action by acting on specific pathways to improve metabolic, ovarian, and hormonal functions and levels. The study was relatively small with 50 women, who were also overweight. Both groups (one group receiving myo-inositol and the other group receiving D-chiro-inositol) showed improvement in predefined metabolic parameters, and that a combination of the two proved more effective than those who just received one type following three months of treatment.
As a result, the study determined that combined myo-inositol and D-chiro-inositol in a ratio of 40:1 can, and should be, a first-line approach in the treatment of overweight PCOS patients, in effect reducing the risk of metabolic syndrome (12).
In 2014, an update was published (“Updates on myo-inositol plus D-chiro-inositol combined therapy in polycystic ovary syndrome“) that verified benefits were effective in PCOS treatments, although myo-inositol had a beneficial effect on reproductive functions while the combination, at least in clinical settings, showed the ability to reduce insulin resistance, cardiovascular risk, and blood levels of androgens as well as its ability to regulate menstrual cycles along with spontaneous ovulation (13).
What About Side Effects?
Taking dosages in excess of 50 mg can contribute to flushing, which is caused by a temporary dilation of peripheral blood vessels, triggered by an initial and quite a large release of histamine. It’s harmless, but can be frustrating. A number of timed release products have been found on market shelves in recent years, and while they may diminish the issue of skin flushing, they may be linked to increased risk of liver damage as well as other serious side effects.
It should also be noted that recommendations for oral doses may also depend on the condition being treated as well as its severity. Inositol also works well with other methyl donors and till date, no additional interactions have been verified. Following are a few general recommendations:
- Panic disorder – 12 to 18 g daily
- Obsessive-compulsive disorders – 18 g daily
- Polycystic ovarian syndrome symptoms – 1,200 mg per day (D-chiro-inositol)
- Psoriasis associated with lithium treatments – 6 g daily
- General liver support – 100 mg to 500 mg daily
- Diabetes treatment (always confer with a physician first) – 1,000 to 2,000 mg daily
- Depression – 12 g daily
Such recommendations may differ based on age, weight, status, as well as expected treatment goals and outcomes. Till date, a recommended dietary allowance for inositol has not yet been determined. The average advice for daily consumption approximates 1,000 mg for adults, although higher doses have been recommended in the treatment of a number of medical conditions.
Lack of scientific studies and data have produced little information regarding verified interactions of prescription or other medications with inositol, but caution should always be observed.
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