As many as one in five women suffer from polycystic ovarian syndrome, or PCOS. It is one of the leading causes of infertility, and conventional treatments have bothersome side effects. Could D-chiro-inositol effectively restore a healthy hormone cycle? Read on to learn more.
What Is D-Chiro-Inositol?
The inositols are a family of sugar alcohol molecules with a special role in insulin signaling. Our bodies make them from glucose, the simplest form of sugar. Two of the most important inositols are myo-inositol and D-chiro-inositol, or DCI .
The ratio of myo-inositol to D-chiro-inositol can be used to predict and measure insulin resistance. The more myo-inositol and less DCI in a person’s urine, the more likely they are to be insulin resistant. Researchers are very interested in DCI for this reason .
DCI is important to the machinery of energy production. In the mitochondria, it helps generate energy from sugar. It may also be key to healthy ovarian function [1, 2].
D-Chiro-Inositol vs. L-Chiro-Inositol Isomers
As is the case with amino acids and other organic compounds, D- and L- are used here to give information about a molecule’s orientation in space. In this case, the letters tell us which of chiro-inositol’s six hydroxyl (hydrogen and oxygen) groups are on which “side” of a sugar ring [1, 3].
We’re interested in D-chiro-inositol because it is much more common in our bodies than the L- form [1, 3].
- May restore hormone balance in women with PCOS
- May reduce acne in women with PCOS
- May increase insulin sensitivity
- May prevent diabetes in pregnancy
- Large quantities available from certain foods
- Considered very safe
- May not benefit PCOS women without insulin resistance
- The maximum tolerated dose is unknown
- Not as well studied as myo-inositol
- Combination with myo-inositol is poorly studied
How Does it Work?
D-chiro-inositol makes the hypothalamus region of the brain more sensitive to insulin. This, in turn, changes how the hypothalamus responds to steroid signals and restores a normal LH to FSH ratio in women with PCOS [4, 5].
DCI’s ability to decrease blood sugar may depend on manganese. In a study of diabetic rats, DCI alone did not decrease blood glucose, but a combination of DCI and manganese reduced blood glucose by half .
Similar to insulin, DCI increases the activity of a pathway that reduces blood sugar and promotes the growth of new cells and tissues (PI3K and Akt) .
Unlike insulin, DCI increases AMPK, which then increases energy production. AMPK also blocks an enzyme called NOX4 and activates Nrf2; these changes collectively reduce oxidative stress [8, 9 , 10].
Food Sources of D-Chiro-Inositol
D-chiro-inositol can be found in some foods, possibly at high enough levels to benefit health. Buckwheat and a type of squash called Cucurbita ficifolia (the fig leaf gourd) are particularly high in DCI [11, 12].
In a rat study, the fruit extract of C. ficifolia increased insulin sensitivity; some practitioners of traditional medicine use C. ficifolia to combat diabetes .
Pumpkin seeds also contain a significant amount of DCI .
Potential Benefits of DCI (Possibly Effective)
Scientists are currently investigating whether DCI could improve a number of health conditions, most notably PCOS. DCI has produced positive results in clinical studies for the benefits in this section, but the evidence is not considered strong enough to recommend it just yet, and the FDA has not approved DCI for any medical purpose or health claim. Talk to your doctor before supplementing.
1) Ovarian Function in PCOS
D-chiro-inositol may improve a number of conditions, but the people who have the potential to benefit the most from DCI supplements are women with PCOS.
What is PCOS?
Polycystic ovarian syndrome, or PCOS, is the most common reproductive disorder in women. The criteria for diagnosing this disorder vary widely around the world; as many as 20% of European women have PCOS .
Women with PCOS have too much testosterone compared to estrogen. The main symptoms of PCOS are irregular or absent periods, masculine traits like excess body hair, and enlarged ovaries with cysts. Women with PCOS are often infertile or, at the very least, have difficulty getting pregnant [14, 15].
The Role of D-Chiro-Inositol
PCOS often comes along with other complications like obesity and insulin resistance. In turn, insulin resistance worsens hormone imbalance and often leads to type 2 diabetes. Hence, the diabetes drug metformin is often prescribed to control blood sugar and prevent insulin resistance in women with PCOS .
The cause of insulin resistance in PCOS may be a shortage of D-chiro-inositol; in fact, metformin may work by increasing DCI .
According to limited clinical research, D-chiro-inositol supplements restored regular menstrual cycles, reduce acne, and lower insulin resistance in women with PCOS [17, 18, 19].
Many researchers believe that a combination of D-chiro and myo-inositol may work better than either inositol alone, but the best ratio to take is unknown. Most commercial combined supplements are 40 parts myo- to 1 part D-chiro-inositol [17, 18, 19].
DCI supplements may also restore a healthy ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH), another common marker of PCOS [20, 21].
Hyperandrogenism and Acne
Both myo-inositol and D-chiro-inositol have improved insulin sensitivity and the menstrual cycle in human studies. However, myo-inositol had a stronger effect on insulin and DCI had a stronger effect on hyperandrogenism: the expression and appearance of masculine hormones and traits .
In women with PCOS and other hyperandrogenic disorders, high levels of testosterone (and other “male” hormones) cause excess body hair and acne. DCI supplements lowered these male hormones and helped reduce body hair and clear acne [22, 17].
Diabetes is a well-known metabolic disorder. Type 2 diabetes is characterized by insulin resistance and high blood sugar .
In a clinical trial, combined supplementation with myo-inositol and DCI decreased blood sugar and HbA1c, a measure of long-term blood sugar. At a dose of 1,100 mg of myo-inositol and 27.6 mg of DCI per day, none of the participants had side effects .
In diabetic rats, high doses of DCI alone reduced blood sugar levels by over 20% .
Diabetes during Pregnancy
During pregnancy, women sometimes develop a type of diabetes called gestational diabetes mellitus. Gestational diabetes usually resolves by itself after the pregnancy is over, but meanwhile, it can threaten the health and life of the mother and unborn child [24, 25].
Women with diabetes during pregnancy are at higher risk of giving birth to a premature or unusually large baby with dangerously low blood sugar .
In one study of 40 women at risk of gestational diabetes, supplementation with D-chiro-inositol and myo-inositol significantly reduced blood sugar and risk of high-weight births .
Complications of Diabetes
Diabetes can cause complications like osteoporosis and nerve damage. These conditions reduce the quality of life for people with diabetes, who become more susceptible to breaking bones, nerve pain, fainting when standing up, digestive concerns, and erectile dysfunction [26, 27].
In a cell study, DCI prevented the formation of cells that break down bone tissue. In another promising study, DCI supplements prevented nerve damage in diabetic rats. Unfortunately, these effects have not yet been investigated in humans [28, 29].
Animal & Cell Studies (Lacking Evidence)
No clinical evidence supports the use of DCI for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.
3) Alzheimer’s Disease
21st-century researchers have made a connection between insulin signaling and the progression of Alzheimer’s disease. The brains of people with Alzheimer’s disease tend to be resistant to insulin, and this resistance may lead to degeneration of the basal ganglia .
The connection is so strong that researchers have even started calling Alzheimer’s disease “type 3 diabetes.” Some people at genetic risk of type 2 diabetes also have a higher risk of developing Alzheimer’s [30, 31].
In a cell study, DCI and insulin produced similar results: they both prevented the buildup of toxic beta-amyloid proteins. If these results hold true in clinical trials, DCI may help prevent Alzheimer’s in people with insulin resistance .
Researchers also believe that DCI is able to cross the blood-brain barrier; if this is true, oral supplements of DCI could slow the progression of Alzheimer’s disease .
D-chiro-inositol may be a potent antioxidant and anti-inflammatory. In a cell study, DCI reduced hydrogen peroxide (a strong indicator of oxidative stress) and increased the activity of antioxidant enzymes .
The same study found that DCI reduced tumor necrosis factor-alpha (TNF-a) in fat cells. TNF-a is an inflammatory cytokine, so this result suggests that DCI has mild anti-inflammatory activity. What’s more, DCI boosted the master antioxidant glutathione. Glutathione’s main role is to neutralize excessive oxidative stress .
Another cell study confirms this antioxidant potential. DCI increased the activity of Nrf2, a protein that increases the body’s natural antioxidant defense .
Limitations and Caveats
Some of the research on D-chiro-inositol in PCOS was funded by Insmed Pharmaceuticals. This pharmaceutical company was developing DCI as a drug in the early 21st century, but this research appears to have been suspended .
Fortunately, many of the claims made by researchers with Insmed funding are supported by independent studies without conflicts of interest.
DCI is not as well studied as its close relative, myo-inositol. These two compounds combine well, but the optimal therapeutic ratio is unknown because only the 40:1 ratio has been studied.
Side Effects & Safety
D-chiro-inositol has not reliably produced any side effects. No maximum tolerated dose has been reported, but effective doses of up to 1.2 g per day are considered very safe [23, 17].
In a controversial study, some doses of DCI (up to 2.4 g per day) appeared to reduce the quality of eggs and embryos in women with PCOS.
However, the editors of the Journal of Ovarian Research have expressed concern that this study presents false information and was not approved by ethics committees. Even more strangely, one of the authors of the study later denied having written it [35, 36].
DCI During Pregnancy
According to limited clinical research, combined myo-inositol and DCI could potentially help prevent diabetes during pregnancy in women at risk. Such treatment may actually improve the health outcomes of both mother and child. However, the research is still limited .
Talk to your doctor before using DCI or any other supplements during pregnancy.
There is no safe and effective dose of DCI because no sufficiently powered study has been conducted to find one. The FDA has not approved DCI for any medical purpose or health claim. That being said, clinical trials have found benefits associated with certain amounts of daily D-chiro-inositol.
For D-chiro-inositol alone, doses of between 500 mg and 1.2 g per day improved hormone profiles and restored ovulation. 1 g per day improved egg quality in women undergoing controlled ovarian hyperstimulation .
For combinations of myo-inositol and DCI in the common ratio of 40:1, 550 mg of myo-inositol and 13.8 mg of DCI restored ovulation and increased fertilization rates of PCOS women who were trying to get pregnant .
For diabetes in pregnancy, 1.75 g of myo-inositol and 250 mg of DCI per day reduced blood sugar and health risks for the mother and baby. If you are pregnant and at risk of gestational diabetes, talk with your doctor before supplementing with inositols .
Myo-Inositol and D-Chiro-Inositol Combinations
Many commercial inositol supplements combine myo-inositol and D-chiro-inositol, claiming to mimic their natural ratio in a healthy human body.
A meta-analysis of inositols for women with PCOS found that combined supplements restored ovulation and improved embryo quality and implantation rates. In another study, combined supplements reduced the risk of metabolic disease in women with PCOS more effectively than myo-inositol alone [17, 37].
Unfortunately, no research has yet identified the ideal ratio of myo-inositol to D-chiro-inositol, but the ratio present in commercial supplements (40 parts myo- to 1 part D-chiro-) has, thus far, produced good results [17, 38].
In short: combined supplements with both myo-inositol and D-chiro-inositol may work better than either inositol alone, but no studies have specifically evaluated the combination compared with just one or the other.
D-chiro-inositol, like its close relative myo-inositol, plays a role in the menstrual cycle and is being investigated for its potential in women with polycystic ovarian syndrome (PCOS). D-chiro-inositol could work by increasing sensitivity to insulin and rebalancing hormone signaling in the brain.
Its other promising application is in diabetes, which is often comorbid with PCOS.
Myo-inositol and D-chiro-inositol are often combined in a ratio of 40:1. This combination may improve PCOS symptoms more effectively than either inositol on its own.