By Christopher Tack |
Clinical Specialist Physiotherapist
Inositol is a sugar alcohol from rice bran which is a vitamin-like compound (also known as vitamin B8). It is not one of the better known compounds people worry about or supplement, however it is an important constituent of our cells which is obtained in through our diet.
This article focuses on inositol and its functions within our bodies, and will examine the benefits of its use as a therapeutical supplement.
What Is Inositol?
Inositol is a cyclic carbohydrate which is found in all of our cells.
It is found in high concentration in mother’s milk and is an essential vitamin for babies, however because it can be formed by dextrose (d-glucose) in our bodies, it is not considered an essential nutrient for adults.
There are nine forms of inositol which vary only slightly in the arrangement of their atoms. The most common of these forms is myo-inositol (or cis-1,2,3,5-trans-4,6-cyclohexanehexol) which is the most abundant isomer of inositol found in mammals (predominantly in the central nervous system). Due to its commonality, this form is generally described simply as “inositol” (1).
As a sugar it is not surprising to find that this compound tastes sweet and exhibits about 48% the degree of sweetness of sucrose. However, it has been stated that despite the lesser degree of sweetness, the “sweetness quality” remains similar to that of sugar.
There are a variety of physiological effects of this compound which revolve around the biochemical function of inositol in the membranes of our cells, which facilitate regulation of cellular response and the function of cellular enzymes. We will examine these effects further shortly.
Where can I get Inositol?
Inositol is fairly abundant in a variety of foodstuffs
Including various fruits, vegetables, seeds, beans and grains (particularly oats and bran). Additionally, some forms of nuts contain high levels of this compound. For example, almonds contain 9.4% of their dry weight, and walnuts contain 6.7% (2).
Fruits high in inositol include cantaloupe and citrus fruits (except lemons). For example, 120g of grapefruit juice will contain approximately 470mg of inositol (3).
The average person’s diet in the western world contains 900mg within a calorie allowance of 2500kcal; however the range can vary from 225mg to 1500mg per day per 1800kcal dependent upon the constituent parts of the diet (3).
How does Inositol work?
Prior to outlining the specific benefits of increasing supplementation of inositol, it is important to delineate the specific biological function and role of this compound. Inositol is an important part of the membrane of our cells and has a unique structure which allows it to be distributed and move in and out of cells easily.
This characteristic means it can have a variety of jobs in our body, which it amazingly does by simply responding to the presence of hormones and facilitating onward chemical reactions. This function is described as the second messenger concept.
The second messenger model is where a signalling molecule within the cell responds to the presence of a hormone and triggers physiological reactions which cascade and lead to a specific result. These reactions could include cell differentiation, proliferation or even apoptosis (cell death).
Inositol is a key component to this process and is the source of various “second messengers” (such as the specific isomer inositol-1,4,5-triphosphate which modifies intracellular calcium levels). This role is essential as the hormone itself cannot breach the cell membrane barrier so this sequence is required for the hormone to exhibit its effects across the body tissue.
A good example of this function, which is key to many of inositol’s therapeutic benefits, is how it assists neurotransmitters in the brain because it is able to manipulate the central nervous system without interacting directly with pre and post brain receptors.
One of the ways it manipulates brain function is through regulating the amount of calcium in our cells. Calcium assists a variety of cell functions through signalling pathway reactions. Usually the levels of calcium within the cellular solution are low, however inositol triphosphate released from the cell membrane can travel to a specific part of the cell called the endoplasmic reticulum and facilitate the release of the endoplasmic calcium stores, which in turn releases neurotransmitters (4).
Additionally, inositol also acts as a regulator of osmosis, therefore assisting the regulation of water movement through our central nervous system cells. Both these functions are controlled by managing the levels of inositol in our brain to directly effect the rate of cellular signallig (5).
This is one example of how the biological mechanism of inositol promotes signalling changes in our body. A similar effect is seen in response to insulin release, where inositol is classified as an insulin sensitising agent as those with type 2 diabetes have been shown to exhibit altered urinary clearance of inositol (6). We will examine the most strongly evaluated therapeutic benefits of inositol further.
How can Inositol help me?
A predominant amount of research has examined the role of inositol in the central nervous system due to the abundance of the compound in these cells. This makes sense as due to it’s effects on brain signalling, a change in cellular inositol can eventually lead to the development of neurological disorders.
We will evaluate some of the more commonly researched neurological issues influenced in this way.
Back in 1978 researchers found that the amount of inositol in the cerebrospinal fluid of depressed patients was reduced compared to healthy individuals (7). Later these results were elaborated upon and it was found that the provision of inositol could increase the levels of inositol by up to 70% (8).
Further experiments directly tested whether a 12g daily dose of inositol would benefit depressed patients compared to placebo. One double blind randomised controlled study found a significant improvement in the Hamilton Depression Rating Scale, indicating a reduction in depressive symptoms and the impact of depression of the individual’s life (9).
Another study showed also that a 12g dose demonstrated an effective anti-depressant effect, and that additionally when participants stopped taking inositol, half of the group relapsed back into depression (10). These studies show a definite therapeutic potential for inositol in assisting brain signalling in those with depression.
Another area where brain signalling shows deficiency is in Alzheimer’s disease. This is a neurological disorder where brain function deteriorates due to a generalised degeneration of brain tissue. It is the leading cause of dementia.
In 1996 a group of 11 individuals with the diagnosis of Alzheimer’s disease underwent a trial which compared the provision of 6g of inositol daily to a placebo supplement. They took this dose for 30 days to examine the effects on their symptoms which included dementia (11).
The participants were evaluated using a comprehensive assessment tool called the Cambridge Mental Disorder of Elderly Examination (CAMDEX) which measured various effects of the disease on the individual including physical and mental state and cognition.
The results of this study were interesting as they showed that the provision of inositol showed an increase in the cognitive score of 9 points on the scale, whereas placebo only increased by 4 points. The significant improvements in the cognition score were found particularly in language and orientation. Thus indicating that inositol may assist cellular signalling even in those where physiological capacity of the tissue was degenerate.
Obsessive Compulsive Disorder
Obsessive compulsive disorder (OCD) is a mental health condition where a person exhibits compulsive behaviour and suffers from obsessive thoughts. These traits leave the person prone to anxiety, disgust and psychological stress. An underlying physiological change in people with this disorder is the reduction in serotonin in their brains, which is key neurotransmitter which contributes to feelings of happiness and wellness (12).
Due to serotonin being one of the neurotransmitters which is influenced by a form of inositol as a second messenger (specifically phosphatidylinositol), experiments have been undertaken to examine the benefit of inositol provision compared to placebo in double blind, placebo controlled trials.
One such trial examined the benefits of 18g of inositol in those suffering from OCD over a period of 6 weeks (13). The results indicated a significant improvement in obsessive thoughts and compulsive behavioural traits using a tool called the Yale-Brown Obsessive Compulsive Scale. In fact the improvements in this scale were comparable to serotonin reuptake inhibitor anti-depressant medications, fluvoxamine and fluoxetine. This would indicate that in the case of those with OCD, inositol’s function as a second messenger is similar in effectiveness as widely used medications.
Another interesting area of brain function examined, in regards to the benefits of inositol, is pain relief. In a study of 24 people having their gallbladders removed, a specific isomer of inositol was provided (inositol-1,2,6-triphosphate) alongside opioid pain killers in some subjects (14). This specific group of individuals were given a dose of 240mg of inositol initially, followed by 90mg per hour for 24 hours post surgery.
Incredibly, the amount of opiates used in this group was significantly lower than the control group (who were just given saline) for the first 3 days. Additionally, this group had a significant reduction in pain for the first 5 days measured on a visual analogue rating scale (compared with the control group).
Further research has suggested that the use of inositol provide these benefits by perhaps enhancing the effectiveness of the post surgical opiate analgesics (15).
Other Therapeutic Benefits
Alongside the changes seen in brain function through the second messenger role of inositol, other physiological benefits have been found.
As previously mentioned the presence of inositol can have an influence on the degree of insulin sensitivity in those with diabetes. It has been found that the provision of an inositol compound has the ability to reduce or prevent insulin resistance, particularly in ladies with polycystic ovary syndrome or pregnant women with gestational diabetes.
Studies show that providing 2g of inositol per day (as part of a controlled diet) for pregnant women with gestational diabetes, leads to improved fasting serum insulin and improved blood glucose levels (16). These changes indicate an improvement in the Homeostatic Model Assessment Index (a measure used to quantify insulin resistance) by 21% (compared to diet alone).
Prevention of Metabolic Syndrome
Another area closely linked with such changes in resistance to insulin is metabolic syndrome, and specifically the role of inositol on preventing lifestyle disease components of this syndrome (e.g. obesity and hyperlipidaemia).
One such study (17) examined this relationship in metabolic disease patients by providing a dosage of inositol (5g per day for one week, 10g per day for the second) and measuring the effect on various blood fat parameter levels (e.g. low density lipoprotein, small dense lipoprotein and apolipoprotein).
The results of this study demonstrated a 22% reduction in small, dense low density lipoprotein (sdLDL) alongside a significant elevation of serum plasmalogen. This is in addition to a significant reduction in blood glucose level.
These changes in blood fat levels are indicative of an improvement of metabolic disease status as sdLDL is considered an emerging risk factor for cardiovascular disease, and deficiency in plasmalogen is considered a valid biomarker for vascular health. Thus showing that the role inositol places in health is not restricted to the nervous system.
Inositol Safety/Side Effects
Inositol has a lethal dose of 10,000mg per kg of bodyweight in mice (18) indicating that therapeutic doses are well tolerated and safe in animals.
Human studies indicated that doses up to 18g per day for 3 months or 2g per day for a whole year and safe and well tolerated (19). When side effects do present they are generally mild and related to the gastrointestinal system (e.g. nausea, flatulence and diarrhoea) (20).
However there are population groups where use of inositol is either cautioned against or contraindicated. For example, in some children with attention deficit hyperactivity disorder inositol showed no therapeutic benefit and actually caused a worsening of the disorder (21).
There is also suggestions that inositol may have an adverse effect during pregnancy. Specifically, the release of calcium stores via the inositol second messenger function can stimulate uterine contractions (22-23).
The most commonly utilised supplementary dosage of inositol is 0.5-2g per day.
However, dosages of up to 12g daily are utilised in some conditons (such as depression).
Take Home Message
The unusual biochemical function of inositol makes it a worthy supplement for your attention. Whilst no supplement should replace the medication prescribed by a doctor, in some cases some compounds can be useful as a therapeutic alternative.
Discuss inositol with your doctor if you felt you may benefit from its use therapeutically.
Alternatively this pseudovitamin can be utilised for otherwise healthy individuals who want to improve their insulin sensitivity, assist management of blood fats or to assist with stress and anxiety!