Inositol / IP6

 Longevity:

• Extended the lifespan of C Elegans by activating daf-18 (Pten). Alters lifespan via mitophagy regulator PTEN induced kinase-1 (pink-1) and mitophagy. Promotes mouse healthspan (ref).

• Extended the lifespan of fruit fly through anti-oxidant and other effects. (ref)

Metabolic effects:

• Myo-inositol is a vitamin-like compound that cells in the body require to generate energy and burn fat. Uses cases: Ref.

• Inositol supplementation decreased blood glucose through an improvement in insulin sensitivity that is independent of weight. HOMA-IR (MD −1.96 mmol × mUI/l, 95% CI −2.62, −1.30). (ref)

• Supplementation significantly decreased SBP and DBP. SBP (WMD − 5.69 mmHg; 95% CI − 7.35 to − 4.02, P < 0.001) and DBP (WMD − 7.12 mmHg; 95% CI − 10.18 to − 4.05, P < 0.001). (ref)

• Supplementation significantly decreased BMI (WMD = −0.41 kg/m2; 95% CI: −0.78, −0.04; p = 0.028). (ref)

• in vitro, IP6 reduced the formation of advanced glycation end-products (AGEs). T2D who supplemented with IP6 had lower levels of circulating AGEs and HbA1c. (ref)

• Daily 4 g dose of inositol plus 400 microg of folic acid improved erectile dysfunction in diabetic men. In a separate study, IP6 alone lowered LH, FSH and increased Testosterone in males. (ref)

• Modestly improved mental health (mood and anxiety).

• High doses (usually in the 12-18g range) are required for any neurological effects while lower doses (2-4g) are sufficient for fertility and insulin sensitizing effects.

Effects on cancer:

• IP(6) had a dose-dependent cytotoxic effect on leukaemic haematopoietic cells.

• IP6 + Inositol was helpful in a study with 14 breast cancer patients for reducing the side effects of chemotherapy (didn’t have drop in leukocyte and platelet counts) and preserving the quality of life (improved functional status, p = 0.0003).

• In a separate trial with 20 breast cancer patients, topical IP6 on the breast significantly improved the quality of life and functional status. A significant difference between was observed in WBC and PLT count.

• Supplementation reduced pre-cancer lung lesions in a human RCT. 

• Myo-inositol is increased in people with lymphomas, brain, and spinal cord tumors. Supplementing in those cases may be counterproductive (ref).

Effects of inositol on glucose homeostasis: Systematic review and meta-analysis of randomized controlled trials, 2019

Background & aims

The effect of inositol on glucose homeostasis is not well characterized. The aim of the present meta-analysis is to synthesize the effects of inositol on glucose homeostasis in different clinical conditions.

Methods

We performed a systematic review (CRD42017057927) following PRISMA guidelines. Web of Science and Medline were searched for randomized controlled trials (RCTs) that addressed supplementation with compounds of the inositol family in humans and assessed their effects on glucose homeostasis.

Results

We screened 476 abstracts and included 20 RCTs with a total of 1239 subjects. Meta-analysis showed in the treatment arm a reduction in fasting plasma glucose (Mean difference (MD) −0.44 mmol/l, 95% CI −0.65, −0.23), 2 h PG after 75 g OGTT (MD −0.69 mmol/l, 95% CI −1.14, −0.23), abnormal glucose tolerance (Relative risk (RR) 0.28, 95% CI 0.12, 0.66), fasting insulin (MD −38.49 pmol/l, 95% CI −52.63, −24.36), and HOMA-IR (MD −1.96 mmol × mUI/l, 95% CI −2.62, −1.30). No differences were observed in BMI, HbA1c and % of patients requiring insulin treatment. Sensitivity analysis did not change treatment estimates. Mention to adverse events was only present in 13 articles with no sign of seriousness.

Conclusions

Inositol supplementation decreases blood glucose through an improvement in insulin sensitivity that is independent of weight. Assessment of adverse effects is scarce among published trials and should be fully addressed before considering inositol as a therapeutic agent for glucose-related outcomes. The characterization of the subjects achieving benefit from the intervention and the formulations to be used should also be known.

The effect of inositol supplementation on blood pressure: A systematic review and meta-analysis of randomized-controlled trials, 2021

Background & aims

Potential effects of inositol supplementation on blood pressure (BP) have been examined in several interventional studies. Nevertheless, findings in this context are controversial. Therefore, the current systematic review and meta-analysis aimed to comprehensively assess the impact of inositol supplementation on BP.

Methods

Five online databases including Web of Science, Scopus, Embase, Cochrane, Google Scholar, and PubMed were systematically searched from inception to March 2020. We included all randomized clinical trials (RCTs) evaluating the effects of inositol supplementation on systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) in humans.

Results

The random-effects meta-analysis of 7 eligible RCTs demonstrated the significant decline in both SBP (WMD − 5.69 mmHg; 95% CI − 7.35 to − 4.02, P < 0.001) and DBP (WMD − 7.12 mmHg; 95% CI − 10.18 to − 4.05, P < 0.001) following supplementation with inositol. Subgroup analysis showed that studies performed in individuals with metabolic syndrome with a longer duration (>8 weeks) and a dose of 4000 mg resulted in a more effective reduction in SBP and DBP with acceptable homogeneity.

Conclusions

The current meta-analysis, indicated that supplementation with inositol significantly decrease SBP and DBP. Further large-scale RCTs with better design are needed to confirm these findings.

Inositol supplementation and body mass index: A systematic review and meta-analysis of randomized clinical trials, 2021

Background

Inositol is a sugar-alcohol and recognized as a key component of cell membrane phospholipids. It has crucial role in the cell signaling pathways and contribute to improving glycemic responses. Although some earlier studies have revealed the effect of inositol mediating glucose uptake by improving insulin sensitivity, the benefit of inositol supplementation in patients with overweight and obesity is not completely understood. This study aimed to assess the impact of inositol supplementation on body mass index (BMI) through a systematic review and meta-analysis of controlled clinical trials.

Methods

A systematic search was performed to August 2021 in the following databases: PubMed-Medline, Embase, Web of Science and Scopus. Fifteen controlled clinical trials investigating the effect of inositol on adult's BMI were finally included in the study. A random-effects model was employed to estimate the effect size. Subgroup analysis was performed by dose, duration, age, type of inositol. Meta-regression was used to investigate presence of any linear relationship. Begg's and Egger's tests were carried out to detect small study effect.

Results

The results of pooled analysis showed that inositol supplementation significantly decreased BMI scores (WMD = −0.41 kg/m2; 95% CI: −0.78, −0.04; p = 0.028). Subgroup analysis was performed to identify the source of heterogeneity among studies (I2 = 73.9%, p < 0.001), demonstrating supplementation duration, baseline BMI, mean age of participants, type of inositol and dosage were potential sources of heterogeneity. The effect of intervention was more clinically significant in participants with polycystic ovary syndrome (PCOS) and overweight/obesity. Inositol in the form of myo-inositol (MI) had stronger effect on BMI reduction.

Conclusion

The meta-analysis suggests that oral inositol supplementation has positive effect on BMI reduction. Inositol supplementation could be considered as an adjunct treatment to improve body mass index.

Examine (link)

Inositol is a word that collectively refers to molecules with a similar structure, a collection of nine stereoisomers. While the term 'inositol' is used commonly with dietary supplements, it usually refers to a specific stereoisomer called myo-inositol. Inositols are pseudovitamin compounds that are falsely said to belong to the B-complex family, and are found in most foods but in highest levels in whole grains and citrus fruits.

Myo-inositol shows the most promise as a dietary supplement for promoting female fertility, restoring insulin sensitivity in instances of resistance (type II diabetes and polycystic ovarian syndrome being the most well investigated), and for reducing anxiety as well. Due to the mixed benefits to insulin resistance and fertility, myo-inositol is considered a good treatment for PCOS in women.

It also holds some promise as an anti-depressant (although not as impressive as its anxiolytic and anti-panic effects) and against some other conditions associated with anxiety such as panic disorders and binge eating. It is relatively ineffective for schizophrenia and autism, and has failed in treating PTSD despite its anti-panic effects.

In part because of its benefits to fertility and PCOS, as well as the anxiolytic effects potentially helping symptoms of PMS (dysphoria and anxiety mostly), myo-inositol is sometimes referred to as a general female health supplement. At times, the anti-depressant effects associated with this supplement seem to only work in females with males having no benefit.

It is a very safe supplement to ingest, and all side-effects associated with myo-inositol are merely mild gastrointestinal distress from high doses. High doses (usually in the 12-18g range) are required for any neurological effects while lower doses (2-4g) are sufficient for fertility and insulin sensitizing effects.

IP-6, 2021

IP-6, inositol hexaphosphate, is a vitamin-like substance. It is found in animals and many plants, especially cereals, nuts, and legumes. It can also be made in a laboratory.

Some people use IP-6 to treat and prevent cancer, including prostate cancer, breast cancer, colon cancer, liver cancer, and blood cancers. Researchers have been studying the role of IP-6 in cancer treatment and prevention since 1988. A book called "IP-6, Nature's Revolutionary Cancer-Fighter" by prominent IP-6 researcher Abulkalam M. Shamsuddin, MD, Ph.D, has popularized IP-6 as an anti-cancer tool.

IP-6 is also used for boosting the immune system, treating anemia, and preventing heart disease and kidney stones.

In manufacturing, IP-6 is added to food to keep it from spoiling.

How does it work?

IP-6 might help treat and prevent cancer by slowing down the production of cancer cells. It might also bind to certain minerals, decreasing the risk of colon cancer. IP-6 is also an antioxidant.

Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells, 2002

Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.

Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study, 2010

Background: Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy.

Patients and methods: Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life.

Breast cancer patients receiving chemotherapy, who took IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities.

Conclusion: IP6 + Inositol was helpful in a study with 14 breast cancer patients for reducing the side effects of chemotherapy (didn’t have drop in leukocyte and platelet counts) and preserving the quality of life (improved functional statu, p = 0.0003).

Phytate Decreases Formation of Advanced Glycation End-Products in Patients with Type II Diabetes: Randomized Crossover Trial, 2018

Myo-inositol hexaphosphate (phytate; IP6) is a natural compound that is abundant in cereals, legumes, and nuts and it has the ability to chelate metal cations. The binding of IP6 to transition metals suggests that it could be used for the treatment of metal-catalyzed protein glycation, which appears to trigger diabetes-related diseases. Our in vitro studies showed that IP6 reduced the formation of Fe3+-catalyzed advanced glycation end-products (AGEs). This led us to perform a randomized cross-over trial to investigate the impact of the daily consumption IP6 on protein glycation in patients with type 2 diabetes mellitus (T2DM; n = 33). Thus, we measured AGEs, glycated hemoglobin (HbA1c), several vascular risk factors, and urinary IP6 at baseline and at the end of the intervention period. Patients who consumed IP6 supplements for 3 months had lower levels of circulating AGEs and HbA1c than those who did not consume IP6. This is the first report to show that consumption of IP6 inhibits protein glycation in patients with T2DM. Considering that AGEs contribute to microvascular and macrovascular complications in T2DM, our data indicates that dietary supplementation with IP6 should be considered as a therapy to prevent the formation of AGEs and therefore, the development of diabetes-related diseases in patients with T2DM.

Inositol hexaphosphate (InsP6) as an effective topical treatment for patients receiving adjuvant chemotherapy after breast surgery, 2017

Objective: Oral treatment with inositol hexaphosphate (InsP6) has shown to be efficient in decreasing adverse effects in patients with breast cancer under chemotherapy. This study was aimed at evaluating and comparing the efficacy of topical InsP6 in improving quality of life in women treated with anticancer drugs.

Patients and methods: The study was a double-blind, randomized controlled trial (RCT) with allocation concealment of 20 patients in two groups, one (experimental) applied 4% topical formulation of InsP6 once a day, whereas the second one (control) a gel containing hyaluronic acid. InsP6 therapy started 6 weeks after lumpectomy. Blood tests were monitored in both groups and quality of life was assessed using standardized QLQ-C30 and QLQ-BR23.

Results: Patients who applied InsP6 on the breast significantly improved their quality of life and functional status reducing side effects compared to control group; moreover, after treatment, a significant difference between the two groups was observed in the white blood cells and platelets count values.

Conclusions: Topical InsP6 treatment has demonstrated to be effective and safe in preventing and/or mitigating chemotherapy-induced side effects as well as the preserving quality of life in women with ductal breast cancer.

A phase I study of myo-inositol for lung cancer chemoprevention, 2006

Introduction: A phase I, open-label, multiple dose, dose-escalation clinical study was conducted to assess the safety, tolerability, maximum tolerated dose, and potential chemopreventive effect of myo-inositol in smokers with bronchial dysplasia.

Materials and methods: Smokers between 40 and 74 years of age with >or= 30 pack-years of smoking history and one or more sites of bronchial dysplasia were enrolled. A dose escalation study ranging from 12 to 30 g/d of myo-inositol for a month was first conducted in 16 subjects to determine the maximum tolerated dose. Ten new subjects were then enrolled to take the maximum tolerated dose for 3 months. The potential chemopreventive effect of myo-inositol was estimated by repeat autofluorescence bronchoscopy and biopsy.

Results: The maximum tolerated dose was found to be 18 g/d. Side effects, when present, were mild and mainly gastrointestinal in nature. Using the regression rate of the placebo subjects from a recently completed clinical trial with the same inclusion/exclusion criteria as a comparison, a significant increase in the rate of regression of preexisting dysplastic lesions was observed (91% versus 48%; P = 0.014). A statistically significant reduction in the systolic and diastolic blood pressures by an average of 10 mm Hg was observed after taking 18 g/d of myo-inositol for a month or more.

Conclusion: myo-Inositol in a daily dose of 18 g p.o. for 3 months is safe and well tolerated. The potential chemopreventive effect as well as other health benefits such as reduction in blood pressure should be investigated further.

Erectile Dysfunction in Diabetes

Diabetes can cause erectile dysfunction in men. A combination of myo-inositol and folic acid improved erectile dysfunction in 176 men with type 2 diabetes. All men took 4 g/day of inositol and 400 μg/day of folic acid [28].

Myoinositol/folic acid combination for the treatment of erectile dysfunction in type 2 diabetes men: a double-blind, randomized, placebo-controlled study, 2006

Erectile dysfunction is a common complication of diabetes. Diabetes can cause neuropathy or damage to nerves throughout your body, including the penis. Damaged nerves can't communicate properly. So even though you might be emotionally stimulated to have intercourse, nerve damage means that information isn't relayed to the penis, and it doesn't respond. In addition, poor blood sugar control can inhibit nitric oxide production. Lack of nitric oxide can prevent the pressure of blood in the corpora cavernosa from rising enough to close off penile veins, allowing blood to flow out of the penis instead of remaining trapped for an erection. This prospective, randomized, double-blind, placebo-controlled study included 176 patients with type 2 diabetes. The daily 4 g dose of inositol plus 400 microg of folic acid or placebo was divided and given in three doses. The present study demonstrates that Myoinositol/folic acid combination, deserves consideration as therapeutic agent for preventing and treating erectile dysfunction in diabetic men, probably by virtue of both their chronic metabolic, acute ROS scavenging, and NO protective beneficial effects.

Effects on Fertility in Men

The fertility-enhancing effects of myo-inositol are also being researched in men, though it’s too early to draw any conclusions. Additional clinical research is needed to determine if myo-inositol is safe and effective for male infertility.

In 194 men with infertility due to an unknown cause, myo-inositol improved sperm quality, sperm count, and fertility after 3 months. It balanced reproductive hormone levels, reducing LH and FSH, and slightly increasing testosterone. All men took 2 g/day of myo-inositol and 200 μg/day of folic acid [72].

Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: a prospective double-blind randomized placebo-controlled study, 2015

A total of 194 patients were randomized at baseline to receive MI (4 g/day, n = 98) or placebo (n = 96) for 3 months.

Male infertility is a multifactorial disorder that affects a significant percentage of couples. Its etiology and pathogenesis remain elusive in about one-third of the cases; this is referred to as idiopathic infertility. Inositols mediate the sperm processes involved into oocyte fertilization, such as penetration of the ovum cumulus oophorus, binding with the zona pellucida and the acrosome reaction. The aim of this double-blind, randomized, placebo-controlled trial was to evaluate the efficacy and safety of myoinositol (the most abundant form of inositols present in nature) treatment in men with idiopathic infertility. To accomplish this, we evaluated the effects of myoinositol on sperm parameters and reproductive hormones at baseline and after 3 months of treatment in men with idiopathic infertility. No adverse reaction was observed. Myoinositol significantly increased the percentage of acrosome-reacted spermatozoa, sperm concentration, and total count and progressive motility compared to placebo. In addition, myoinositol rebalanced serum luteinizing hormone, follicle-stimulating hormone, and inhibin B concentrations. The clinical improvement of idiopathic infertile patients should encourage myoinositol use for the treatment of this disorder, even though its detailed mechanisms at the testicular level remain still unclear.

Effect of inositol hexaphosphate-loaded red blood cells (RBCs) on the rheology of sickle RBCs, 2013

Conclusion: Our results support the fact that IHP-RBCs could be useful in SCA by decreasing RBC aggregation and blunting the adverse effects of hypoxia on RBC deformability and blood viscosity.

Protection against cancer by dietary IP6 and inositol, 2006

Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.

Antiplatelet activity of inositol hexaphosphate (IP6)

Platelet adhesion to endothelial cells, their aggregation and subsequent release of platelet-derived mediators are key steps in the pathogenesis of thrombosis and atherosclerosis. Using impedance technology the effect of inositol hexaphosphate (IP6) on platelet aggregation and adenosine triphosphate (ATP) release were simultaneously measured in whole blood obtained from healthy volunteers (n = 10). The platelets were activated with adenosine diphosphate (ADP) (10 microM), collagen (2 micrograms/mL), or thrombin (1 U/mL) in the presence or absence of IP6. IP6 significantly inhibited platelet aggregation induced with all agonists in a dose-response manner (p < 0.0001 for ADP and collagen, p = 0.0103 for thrombin), with the IC50 values of 0.9, 1.6 and 0.8 mM. Secretion of platelet dense granule content was measured in parallel. IP6 strongly and significantly reduced agonist-induced ATP release (p = 0.00247 for ADP; p = 0.0074 for collagen; p = 0.0069 for thrombin). These data demonstrate that IP6 effectively inhibits human platelet aggregation in vitro, suggesting its potential in reducing the risk for cardiovascular disease.

D-chiro-Inositol and Pinitol Extend the Life Span of Drosophila melanogaster, 2012

D-chiro-inositol, a member of the inositol family, and pinitol, a 3-methoxy analogue of D-chiro-inositol, have been proposed to have antidiabetic, antiinflammatory, anticancer and stamina enhancing effects. We found that supplementing the diet of Drosophila with D-chiro-inositol and pinitol extended adult longevity in both male and female flies. Life span extension was accompanied by protection against oxidative and starvation stresses, improvement in health span, and no reduction in fecundity. Pinitol increased the fly life span, both in dietary restriction and in ad libitum conditions, suggesting that pinitol increased life span in a manner that was independent of the dietary restriction pathway. Nuclear localization of dFOXO increased in D-chiro-inositol and pinitol-fed flies when compared with controls. Pinitol treatment significantly activated JNK and S6K, but not AKT, indicating that the activation of dFOXO by pinitol is acquired by the activation of S6K and JNK signaling. Hence, our study indicated that D-chiro-inositol and pinitol could be novel food-derived antiaging compounds.

inositol, the secret of longevity, 2020

The loss of homeostasis and the general failing of physiological functions are the main character of aging in organisms, together with various degenerations and increased rates of mortality. Since there are few researches focusing on endogenous metabolic intermediates - metabolites. Jing-Dong J. Han’s team of Peking University used C. elegans as lifespan model, conducted a worm metabolite screen and then identified an eukaryote conserved metabolite, myo-inositol (MI) which extends lifespan, increases mobility and reduces fat content.

By analyzing enzymes in MI metabolic pathway, Han suggests that the longevity effect of MI is dependent on the tumor suppressor gene, daf-18 (homologous to mouse Pten), independent of its classical pathway downstream genes, akt or daf-16. MI also alters lifespan via mitophagy regulator PTEN induced kinase-1 (pink-1) and mitophagy. The effect of MI’s anti-age is proved to be conserved in mouse, indicating a conserved mechanism in mammals.

In view of the long-term safety use of MI in human as a supplement and conclusion on its anti-aging benefits extending from worms to mice through highly a conserved metabolic and signaling pathway present in human, it’s leaving us a potentiality of MI supplementation to promote healthy human aging.

References:

Shi, D., Xia, X., Cui, A. et al. The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16. Nat Commun 11, 4496 (2020). https://doi.org/10.1038/s41467-020-18280-4

Inositol Administration Reduces Oxidative Stress In Erythrocytes Of Patients With Polycystic Ovary Syndrome (link)

Supplementation of myo-inositol at 2g twice daily for the course of one year in postmenopausal women with metabolic syndrome was associated with improvements on all metabolic parameters measured (cardiovascular health and glucose metabolism) although no influence on weight was noted.

One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome, 2012

Objective: To evaluate the 12-month effect of myo-inositol treatment on some biochemical parameters of women affected by metabolic syndrome.

Methods: Eighty outpatient postmenopausal women, affected by metabolic syndrome, were enrolled in a 12-month study. All women were treated with a low-energy diet, and then they were randomly assigned to myo-inositol 2 g b.i.d. (n = 40) or placebo (n = 40). All the women were evaluated for serum glucose, insulin, HOMA-IR (Homeostasis Model Assessment-Insulin Resistance), triglycerides, total and high density lipoprotein cholesterol, body mass index (BMI), waist circumference and blood pressure at baseline and after 12 months of treatment.

Results: With the exception of BMI and waist circumference, after 12 months of treatment, all the parameters studied showed a significant improvement in the myo-inositol group compared to the control group. At the end of the study, in the myo-inositol group, the number of women without metabolic syndrome was eight (20%) whereas, in the control group, only one woman no longer had the metabolic syndrome after 12 months of diet.

Conclusions: Myo-inositol might be considered one of the insulin-sensitizing substances in the treatment of metabolic syndrome.

In a year-long clinical study in 80 women with metabolic syndrome, 2 grams of inositol taken twice daily reduced blood triglyceride levels by an average 34% and total cholesterol by 22%. Improvements in blood pressure and blood sugar were also seen.Amazingly, 20% of the women taking inositol supplements no longer met the criteria for metabolic syndrome by the end of the study (24).

Heart Health

Limited evidence suggests that myo-inositol may contribute to heart health and heart disease prevention in people who are overweight, particularly women.

In several clinical studies, myo-inositol supplementation reduced heart disease risk factors in people with metabolic syndrome. It reduced blood pressure, total cholesterol, and triglycerides while increasing HDL cholesterol [75, 76].

A combination supplement with myo-inositol, soy isoflavones, and cocoa polyphenols reduced heart disease risk in 60 postmenopausal women after 6 months. Aside from improving blood fat measurements, it also improved levels of metabolic hormones (resistin and visfatin). Further research is needed [77].

Antioxidant Defense

Myo-inositol boosted the master antioxidant glutathione in blood cells and reduced oxidative stress in 26 women with PCOS [83].

Buckwheat and squash, rich in D-Chiro-Inositol, are antioxidants, according to several animal and cellular studies [84, 85].

Phytochemicals in hepatocellular cancer prevention, 2009

Since the incidence of liver cancer is increasing in the world, it is valuable to develop an effective method for its prevention. Various phytochemicals have been shown to suppress liver carcinogenesis in experimental studies. Using these phytochemicals, a clinical trial was conducted. Combination of carotenoids and myo-inositol was found to prevent hepatocellular carcinoma development in patients with chronic viral hepatitis and cirrhosis.

A meta-analysis of inositol for depression and anxiety disorders

Objective: This study is a meta-analysis of inositol as a treatment for depression and anxiety disorders.

Methods: PubMed, Cochrane Library database, and PsycINFO were searched up to 14 August 2013. A systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials (RCTs) were conducted comparing inositol for depressed or anxiety disorder patients.

Results: Seven RCTs in depression (two bipolar depression studies, one bipolar depression and major depressive disorder (MDD) study, two MDD studies, and two premenstrual dysphoric disorder (PMDD) studies) (n = 242) were identified. Four RCTs in anxiety disorders (two obsessive-compulsive disorder studies, one panic disorder study, and one posttraumatic stress disorder study) (n = 70) were also identified. There were no statistically significant effects of inositol on depressive, anxiety, and obsessive-compulsive symptoms and discontinuation (all-cause, side effects, and worsening psychiatric symptoms). However, inositol had marginally more responders in depression than placebo (p = 0.06), and inositol showed a trend towards superior efficacy for depressive symptoms in patients with PMDD (p = 0.07). Inositol marginally caused gastrointestinal upset compared with placebo (p = 0.06).

Conclusions: Our results suggest that inositol may be beneficial for depressed patients, especially those with PMDD. The main limitation of this report is that a small number of studies were included in this meta-analysis.

Polycythemia Vera and Essential Thrombocythemia Patients Exhibit Unique Serum Metabolic Profiles Compared to Healthy Individuals and Secondary Thrombocytosis Patients, 2021

Most common myeloproliferative neoplasms (MPNs) include polycythemia vera (PV) and essential thrombocythemia (ET). Accurate diagnosis of these disorders remains a clinical challenge due to the lack of specific clinical or molecular features in some patients enabling their discrimination. Metabolomics has been shown to be a powerful tool for the discrimination between different hematological diseases through the analysis of patients' serum metabolic profiles. In this pilot study, the potential of NMR-based metabolomics to characterize the serum metabolic profile of MPNs patients (PV, ET), as well as its comparison with the metabolic profile of healthy controls (HC) and secondary thrombocytosis (ST) patients, was assessed. The metabolic profile of PV and ET patients, compared with HC, exhibited higher levels of lysine and decreased levels of acetoacetic acid, glutamate, polyunsaturated fatty acids (PUFAs), scyllo-inositol and 3-hydroxyisobutyrate. Furthermore, ET patients, compared with HC and ST patients, were characterized by decreased levels of formate, N-acetyl signals from glycoproteins (NAC) and phenylalanine, while the serum profile of PV patients, compared with HC, showed increased concentrations of lactate, isoleucine, creatine and glucose, as well as lower levels of choline-containing metabolites. The overall analysis revealed significant metabolic alterations mainly associated with energy metabolism, the TCA cycle, along with amino acid and lipid metabolism. These results underscore the potential of metabolomics for identifying metabolic alterations in the serum of MPNs patients that could contribute to improving the clinical management of these diseases.

[MICE STUDY] Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies

and Supplementation, 2020

Liver lipid accumulation is a hallmark of non-alcoholic fatty liver disease (NAFLD), broadly associated with insulin resistance. Inositols (INS) are ubiquitous polyols implied in many physiological functions. They are produced endogenously, are present in many foods and in dietary supplements. Alterations in INS metabolism seems to play a role in diseases involving insulin resistance such as diabetes and polycystic ovary syndrome. Given its role in other metabolic syndromes, the hypothesis of an INS role as a supplement in NAFLD is intriguing. We performed a systematic review of the literature to find preclinical and clinical evidence of INS supplementation efficacy in NAFLD patients. We retrieved 10 studies on animal models assessing Myoinosiol or Pinitol deficiency or supplementation and one human randomized controlled trial (RCT). Overall, INS deficiency was associated with increased fatty liver in animals. Conversely, INS supplementation in animal models of fatty liver reduced hepatic triglycerides and cholesterol accumulation and maintained a normal ultrastructural liver histopathology. In the one included RCT, Pinitol supplementation obtained similar results. Pinitol significantly reduced liver fat, post-prandial triglycerides, AST levels, lipid peroxidation increasing glutathione peroxidase activity. These results, despite being limited, indicate the need for further evaluation of INS in NAFLD in larger clinical trials.

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[MEANING UNCLEAR] Inositol Hexakisphosphate Kinase 3 Regulates Metabolism and Lifespan in Mice, 2016

Inositol hexakisphosphate kinase 3 (IP6K3) generates inositol pyrophosphates, which regulate diverse cellular functions. However, little is known about its own physiological role. Here, we show the roles of IP6K3 in metabolic regulation. We detected high levels of both mouse and human IP6K3 mRNA in myotubes and muscle tissues. In human myotubes, IP6K3 was upregulated by dexamethasone treatment, which is known to inhibit glucose metabolism. Furthermore, Ip6k3 expression was elevated under diabetic, fasting and disuse conditions in mouse skeletal muscles. Ip6k3−/− mice demonstrated lower blood glucose, reduced circulating insulin, deceased fat mass, lower body weight, increased plasma lactate, enhanced glucose tolerance, lower glucose during an insulin tolerance test and reduced muscle Pdk4 expression under normal diet conditions. Notably, Ip6k3 deletion extended animal lifespan with concomitant reduced phosphorylation of S6 ribosomal protein in the heart. In contrast, Ip6k3−/− mice showed unchanged skeletal muscle mass and no resistance to the effects of high fat diet. The current observations suggest novel roles of IP6K3 in cellular regulation, which impact metabolic control and lifespan.

[SIGNIFICANCE UNKNOWN] Whole Body Ip6k1 Deletion Protects Mice from Age-Induced Weight Gain, Insulin Resistance and Metabolic Dysfunction, 2022

The characterization of novel proteins and/or pathways involved in metabolism and aging is crucial to understand the mechanisms that regulate these processes, and to develop therapeutic strategies to improve healthspan [6,23]. The use of new mouse models that lack or overexpress a novel gene of interest is particularly useful in this regard. Using various knockout mouse models, we previously discovered the inositol pyrophosphate (5-IP7) biosynthetic enzyme inositol hexakisphosphate kinase 1 (IP6K1) as a novel target in high-fat diet-induced obesity. A family of three IP6Ks synthesizes the biomolecule 5-IP7 in mammals by phosphorylating inositol hexakisphosphate (IP6) [24–28]. IP6K1 regulates metabolic functions of adipose tissue, liver and pancreatic β cells, whereas IP6K3 modulates metabolism of the skeletal muscle [26,29–32]. IP6K1 impairs insulin signaling by inhibiting the insulin effector protein kinase Akt, promoting high-fat diet-induced insulin resistance [33]. Moreover, IP6K1 reduces whole-body energy expenditure by inhibiting adipose tissue browning and thermogenesis [34]. IP6K1 diminishes energy expenditure and

stimulates fatty acid biosynthesis by inhibiting the metabolism enhancing AMP-activated protein kinase (AMPK) [34,35]. IP6K1 also reduces serum levels of the insulin-sensitizing and metabolically favorable adipokine, adiponectin [34,35]. Consequently, high-fat diet-fed, whole-body- or adipocyte-specific Ip6k1-KO mice are protected from obesity, hyperinsulinemia, insulin resistance, and hepatic steatosis [33–35]. Moreover, whole-body- or hepatocyte-specific Ip6k1 deletion protects mice from high-fat and high-cholesterol (Western) diet-induced lipotoxic liver injury and NAFLD/NASH [36]. IP6K1 also promotes insulin secretion from pancreatic β cells [31,32,37]. Accordingly, Ip6k1 deletion diminishes insulin secretion whereas transgenic mice that express a hyperactive IP6K1 display augmented insulin release, congenital hyperinsulinemia, and obesity [32]. In summary, IP6K1regulates metabolism via pleiotropic mechanisms.

P6K3 inositol hexakisphosphate kinase 3 [ Homo sapiens (human) ]

This gene encodes a protein that belongs to the inositol phosphokinase (IPK) family. This protein is likely responsible for the conversion of inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). It may also convert 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.

Inositol Polyphosphate Multikinase (IPMK), a Gene Coding for a Potential Moonlighting Protein, Contributes to Human Female Longevity, 2019

Biogerontological research highlighted a complex and dynamic connection between aging, health and longevity, partially determined by genetic factors. Multifunctional proteins with moonlighting features, by integrating different cellular activities in the space and time, may explain part of this complexity. Inositol Polyphosphate Multikinase (IPMK) is a potential moonlighting protein performing multiple unrelated functions. Initially identified as a key enzyme for inositol phosphates synthesis, small messengers regulating many aspects of cell physiology, IPMK is now implicated in a number of metabolic pathways affecting the aging process. IPMK regulates basic transcription, telomere homeostasis, nutrient-sensing, metabolism and oxidative stress. Here, we tested the hypothesis that the genetic variability of IPMK may affect human longevity. Single-SNP (single nuclear polymorphism), haplotype-based association tests as well as survival analysis pointed to the relevance of six out of fourteen genotyped SNPs for female longevity. In particular, haplotype analysis refined the association highlighting two SNPs, rs2790234 and rs6481383, as major contributing variants for longevity in women. Our work, the first to investigate the association between variants of IPMK and longevity, supports IPMK as a novel gender-specific genetic determinant of human longevity, playing a role in the complex network of genetic factors involved in human survival. View Full-Text