EVIDENCES

Science is in Kobho’s DNA. All our products have been designed to offer scientific added value. Our selection of ingredients is supported by studies that prove their effectiveness.

Below, you will find a selection of studies that have shown the effectiveness of the ingredients used in our Kobho products.

1. ALPHA-LIPOIC ACID

Study: “Enantio-selective pharma-cokinetics and bioavailability of several racemic α-lipoic acid formulations in healthy volunteers”.

This study found that the absolute bio-availability of the R enantiomer of α-LA was shown to be significantly higher compared to the values that could be achieved for S- α-LA.

The objectives were to study the pharmacokinetics and the absolute bioavailability of the enantiomers of α-lipoic acid (α-LA), also known as alpha-lipoic acid (ALA), for the first time, from various dosage forms. They have been studied for the first time in 12 healthy volunteers using a specific enantioselective HPLC assay.

Single dose of 200 mg racemic α-LA were administered orally (4 tablets each containing 50 mg, 200 mg tablet, and oral solution), in random order. The apparent volume of distribution (Vt) of both enantiomers, in contrast was not significantly different from each other (R (+)-: 419±369 ml kg−1; S (−)-: 471±338 ml kg−1; P=0.424). After oral dosage, C max was observed at 0.21±0.07 h for the oral solution, at 0.70±0.41 h, for the 50 mg tablet, and at 0.90±0.74 h for the 200 mg tablet formulation, with apparently no differences among the enantiomers within each formulation. The t1/2 for all oral dosage forms was comparable to the IV administration. Highest Cmax values were observed for the OS with 1.95 μg ml−1 for R- and 1.17 μg ml−1 for S- α-LA. The AUC of the oral solution showed similar differences between both enantiomers with 0.65 μg·h ml−1 for the R- and 0.37 μg·h ml−1 for the S-form. The absolute bio-availability (Fabs) of the enantiomers from the oral solution was calculated to be 38±15 and 28±14% for R- and S- α-LA, respectively. The results of both tablet forms with respect to the pharma-cokinetic behavior of both enantiomers was in accordance with the results of the oral solution. From both solid dosage forms, Fabs was calculated to be about 25 and 20% for the R - and S-enantiomer, respectively. In general, this observation was applicable and independent from the galenical formulations used.

REFERENCES
  • Hermann, R.et al. (1996) “Enantioselective pharmacokinetics and bioavailability of different racemic α-lipoic acid formulations in healthy volunteers,”European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences, 4(3), pp. 167–174. doi: 10.1016/0928-0987(95)00045-3.

2. ASTAXANTHIN + COQ10

Study: “Astaxanthin improves glucose metabolism and reduces blood pressure in type-2 diabetes mellitus patients”

This study revealed that supplementation with astaxanthin contributes to the improvement of cardiovascular health.

The aim of this randomized placebo-controlled trial was to research the potential effects of astaxanthin (AST) supplementation on the adiponectin concentration, lipid peroxidation, glycemic control, insulin sensitivity, and anthropometric indexes in type-2 diabetes mellitus participants . 44 type-2 diabetes mellitus participants attended the test.

The 8-week administration of AST supplementation increased the serum adiponectin concentration and reduced visceral body fat mass, serum triglyceride, very low-density lipo-protein-cholesterol concentrations, and systolic-blood pressure. Furthermore, AST significantly reduced the fructo-samine concentration and marginally reduced the plasma glucose concentration. This study demonstrated that why type-2 diabetes mellitus participants often have hyper-triglycemia and uncontrolled glucose metabolism. Our findings of dual beneficial effects are clinically valuable. Our results may provide a novel complementary treatment with potential impacts on diabetic complications without adverse effects.

 

Study: “Selenium and Coenzyme Q10 Intervention Prevents Telomere Attrition with Association to Reduced Cardiovascular Mortality - Sub-Study of a Randomized Clinical Trial”

This study found that coenzyme Q10 and selenium supplementation prevents telomere shortening.

This double-blind, placebo-controlled, randomized trial determined whether supplementation with selenium and Q10 coenzyme, also known as ubiquinone prevented telomere attrition and increased cardiovascular mortality.

Short telomeres have been associated with aging and cardiovascular disease. At baseline, leukocyte telomere length (LTL) was 0.954 in the active treatment group and 1.018 in the placebo group (p = 0.23). At 42 months, less shortening of LTL was observed after active treatment compared to placebo (+0.019 vs. -0.129, respectively, p = 0.02) with a significant difference in change basing the analysis on individual changes in LTL. Subjects suffering future death presented with significantly shorter LTL at 42 months than survivors with a significant difference in change of LTL according to cardiovascular mortality and survival. To conclude, LTL preservation after selenium and associated Q10 coenzyme supplementation reduced cardiovascular mortality.

REFERENCES

  • Opstad TB, Alexander J, Aaseth JO, Larsson A, Seljeflot I, Alehagen U. Selenium and Coenzyme Q10 Intervention Prevents Telomere Attrition, with Association to Reduced Cardiovascular Mortality-Sub-Study of a Randomized Clinical Trial. Nutrients. 2022 Aug 15;14(16):3346. doi: 10.3390/nu14163346. PMID: 36014852; PMCID: PMC9412367.
  • Mashhadi NS, Zakerkish M, Mohammadiasl J, Zarei M, Mohammadshahi M, Haghighizadeh MH. Astaxanthin improves glucose metabolism and reduces blood pressure in patients with type 2 diabetes mellitus. Asia Pac J Clin Nutr. 2018;27(2):341-346. doi: 10.6133/apjcn.052017.11. PMID: 29384321.

3. HAIR & NAIL BOOSTER

“Scientific Opinion on the substantiation of health claims related to biotin and energy-yielding metabolism (ID 114, 117), macronutrient metabolism (ID 113, 114, 117), maintenance of skin and mucous membranes (ID 115), maintenance of hair (ID 118, 2876) and function of the nervous system (ID 116) pursuant to Article 13(1) of Regulation (EC) No 1924/2006”

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition, and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of (EC) Regulation No. 1924/2006. This opinion addresses the scientific substantiation of health claims in relation to biotin and the following claimed effects: energy-yielding metabolism, macronutrient metabolism, skin and mucous membrane maintenance, hair maintenance, and nervous system function. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 (Health Claims) and references that EFSA has received from Member States or directly from stakeholders. The food constituent that is the subject of the health claims is biotin, which is a well-recognized nutrient. It is measurable in foods by established methods.

The Panel considers that biotin is sufficiently characterized. The Panel concludes that a cause-and-effect relationship has been established among the dietary intake of biotin and normal energy-yielding metabolism, normal macronutrient metabolism, maintenance of normal skin and mucous membranes, maintenance of normal hair, and normal function of the nervous system. The evidence provided does not establish that inadequate intake of biotin leading to impaired functions of the above-mentioned health relationships occurs in the general EU population.

REFERENCES
  • EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific opinion on the substantiation of health claims related to biotin and energy-yielding metabolism (ID 114, 117), macronutrient metabolism (ID 113, 114, 117), maintenance of skin and mucous membranes (ID 115), maintenance of hair (ID 118, 2876) and function of the nervous system (ID 116) pursuant to Article 13(1) of Regulation (EC) No 1924/2006 on request from the European Commission. EFSA Journal 2009; 7( 9):1209. [17 pp.]. doi:10.2903/j.efsa.2009.1209

4. COLLAGEN + HYALURONIC ACID

Study: “Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study”

This study clearly demonstrated that oral intake of collagen hydrolysate (VERISOL®) has a positive impact on skin health, especially on skin elasticity.

The objective of this research was to study the effectiveness of a specific collagen hydrolysate (CH) (VERISOL®) composed of specific collagen peptides on skin biophysical parameters related to cutaneous aging. In this double-blind placebo-controlled trial, 69 women aged 35–55 years were randomized to receive 2.5 g or 5.0 g of CH, or placebo, once daily, for 8 weeks, with 23 subjects being allocated to each treatment group.

Skin elasticity, skin moisture, trans-epidermal water loss, and skin roughness were objectively measured before the first oral product application (t0), and after 4 (t1) and 8 weeks (t2) of regular intake. Skin elasticity (primary interest) was also assessed at follow-up, 4 weeks after the last intake of CH (t3, 4-week regression phase). At the end of the study, skin elasticity in both CH dosage groups showed a statistically significant improvement in comparison to placebo. After 4 weeks of follow-up treatment, a statistically significantly higher skin elasticity level was determined in elderly women. Moreover, a skin moisturizing effect could be observed in elderly women, although results did not reach a level of statistical significance. In contrast to most topically applied substances, this positive effect of orally applied CH on skin health seems to be long-lasting, especially in women over 50 years of age. It must be stated that the demonstrated efficacy refers to the specific CH composition (VERISOL) used in this study and could not be extrapolated to CH in general. No side effects were noted throughout the study.

REFERENCES
  • Proksch E, Segger D, Degwert J, Schunck M, Zague V, Oesser S. Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. Skin Pharmacol Physiol. 2014;27(1):47-55. doi: 10.1159/000351376. Epub 2013 Aug 14. PMID: 23949208.

5. CURCUMA + BLACK PEPPER

Study: “Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation”

This study found that formulation with phospholipids (Meriva®) improves the human absorption of curcumin due to it.

This randomized double-blind crossover human study researched the relative absorption of a standardized curcuminoid mixture and its corresponding lecithin formulation (curcumin-phospholipid lecithin formulation Meriva®). Clinically validated dosages were used for both products, and plasma levels of all 3 major curcuminoids (curcumin (1a), dimethoxy-curcumin (1b), and bisdemethoxycurcumin (1c)) were evaluated.

Total curcuminoid absorption was about 29-fold higher for Meriva than for its corresponding unformulated curcuminoid mixture, but only phase-2 metabolites could be detected, and plasma concentrations were still significantly lower than those required for the inhibition of most anti-inflammatory targets of curcumin. Remarkably, phospholipid formulation increased the absorption of demethylated curcuminoids, much more than that of curcumin (1a), with significant differences in plasma curcuminoid profile, between Meriva and its corresponding unformulated curcuminoid mixture. Thus, the major plasma curcuminoid after administration of Meriva was not curcumin (1a), but desmethoxycurcumin (1b), a more potent analogue in many in-vitro anti-inflammatory trials. The improved absorption, and possibly also a better plasma curcuminoid profile might underlie the clinical efficacy of Meriva at doses significantly lower than unformulated curcuminoid mixtures.

REFERENCES
  • Cuomo J, Appendino G, Dern AS, Schneider E, McKinnon TP, Brown MJ, Togni S, Dixon BM. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J Nat Prod. 2011 Apr 25;74(4):664-9. doi: 10.1021/np1007262. Epub 2011 Mar 17. PMID: 21413691.

6. MAGNESIUM + VITAMIN B6

Study: “Higher bioavailability of magnesium citrate as compared to magnesium oxide shown by evaluation of urinary excretion and serum levels after single-dose administration in a randomized cross-over study”

This study evidenced a higher bioavailability of the magnesium citrate compared to magnesium oxide.

Since the development of several disorders, such as cardiovascular disease, diabetes, and osteoporosis has been linked to sub-optimal dietary intake of magnesium (Mg), it is important to select the most appropriate Mg compounds for supplement formulation. Therefore, the aims of this study were to research and compare the bioavailability of Mg citrate, an organic Mg compound, and Mg oxide, an inorganic Mg compound. This randomized open cross-over study was conducted in 20 healthy male subjects of Caucasian origin. The bioavailability of both Mg compounds was then assessed by measurement of the renally eliminated Mg quantity, during a 24-hour interval after single-dose Mg administration, as primary endpoint. 

After administration, the renally eliminated Mg quantity was higher for Mg citrate than for Mg oxide. Both quantities were compared by variance analysis (ANOVA), revealing an adjusted mean difference of 0.565 mmol, which was statistically significant at the 5% level (p = 0.0034). Besides, serum Mg concentrations were statistically significantly higher for Mg citrate than for Mg oxide, at several time points after administration. No statistically significant difference was shown in intracellular Mg contents. This study confirms former study results showing a higher bioavailability of the organic Mg compound Mg citrate compared to Mg oxide. It can be concluded that Mg citrate, like other organic Mg compounds may be more suitable than Mg oxide to optimize the dietary magnesium intake.

REFERENCES
  • Kappeler, D., Heimbeck, I., Herpich, C. et al. Higher bioavailability of magnesium citrate as compared to magnesium oxide shown by evaluation of urinary excretion and serum levels after single-dose administration in a randomized cross-over study. BMC Nutr 3, 7 (2017). https://doi.org/10.1186/s40795-016-0121-3

7. MELATONIN + L-TRYPTOPHAN

Study: “Design of multi-particulate “Dome matrix” with sustained-release melatonin and delayed-release caffeine for jet lag treatment”

The objective of this study was to design a multi-particulate formulation of delayed-release melatonin to restore jet lag sleep-wake cycle.

The polymeric pellets were produced using extrusion-spherization technique and fluid-bed coated, when applicable. The compact and dome module were produced by compressing pellets with cushioning agent. Dome matrix was an assembly of modules with pre-determined compact formulation and drug-released characteristics. The physicochemical and in vivo pharma-cokinetics of delivery systems were examined. Melatonin loaded alginate/chitosan-less matrix exhibited full drug release within 8 h gastro-intestinal transit with low viscosity hydroxypropymethylcellulose as cushioning agent. The cushioning agent reduced burst drug release and omission of alginate-chitosan enabled full drug release. Delayed-release alginate-chitosan caffeine matrix was not attainable through polymer coating due to premature coat detachment. Admixing of cushioning agent high-viscosity hydroxypropymethylcellulose and high viscosity ethylcellulose with coat-free caffeine loaded particulates introduced delayed-release response via hydroxypropymethylcellulose swelled in early-dissolution phase and ethyl cellulose sustained matrix hydro phobicity at prolonged phase. The caffeine was released substantially in colonic fluid in response to matrix polymers being degraded by rat colonic content. Dome matrix with dual drug-release kinetics and modulated pharmacokinetics is produced to introduce melatonin-induced sleep phase then caffeine-stimulated wake phase.

REFERENCES
  • Razali, Sharipah; Bose, Anirbandeep; Win Chong, Pee; Benetti, Camillo; Colombo, Paolo; Wui Wong, Tin (2020). Design of multi-particulate Dome matrix with sustained-release melatonin and delayed-release caffeine for jet lag treatment. International Journal of Pharmaceutics, (), 119618–. doi:10.1016/j.ijpharm.2020.119618

8. OMEGA-3

Study: “Bioavailability of marine n-3 fatty acid formulations”

This study found that EPA+DHA in re-esterified triglycerides was the marine n-3 fatty acid formulation with the highest bioavailability.

The present study compares 3 concentrated preparations (ethyl esters, free fatty acids, and re-esterified triglycerides) with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. 72 volunteers were given approximately 3.3 g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks.

After examining increases in the absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bio-availability of EPA+DHA from re-esterified triglycerides was superior (124%) compared to natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA. The use of marine n-3, also known as omega-3, polyunsaturated fatty acids (n-3 PUFA) as supplements can help overcome problems of compliance with recommendations.

REFERENCES
  • Dyerberg J, Madsen P, Møller JM, Aardestrup I, Schmidt EB. Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids. 2010 Sep;83(3):137-41. doi: 10.1016/j.plefa.2010.06.007. PMID: 20638827.

9. PRE, POST AND PROBIOTICS

Study: “Butyrate and Propionate Protect against Diet-Induced Obesity and Regulate Gut Hormones via Free-Fatty Acid Receptor 3-Independent Mechanisms”

This study showed how butyrate and propionate may be an alternative in protecting against diet-induced obesity.

This study examined the effects of short-chain fatty acids (SCFAs) administration in mice, and showed that butyrate, propionate, and acetate all protected against diet-induced obesity and insulin resistance.

SCFAs, primarily acetate, propionate, and butyrate are metabolites formed by gut microbiota from complex dietary carbohydrates. Butyrate and propionate, but not acetate induce gut hormones and reduce food intake. As FFAR3 is the common receptor activated by butyrate and propionate, we examined these effects in FFAR3-deficient mice. The effects of butyrate, and propionate on body weight and food intake are independent from FFAR3. In addition, FFAR3 plays a minor role in butyrate stimulation of glucagon-like peptide-1, and is not required for butyrate and propionate-dependent induction of glucose-dependent insulinotropic peptide. Finally, FFAR3-deficient mice showed normal body weight and glucose homeostasis. Stimulation of gut hormones and food intake inhibition by butyrate and propionate may represent a novel mechanism by which gut microbiota regulates host metabolism. These effects are largely intact in FFAR3-deficient mice, indicating additional mediators are required for these beneficial effects.

REFERENCES
  • Lin HV, Frassetto A, Kowalik Jr EJ, Nawrocki AR, Lu MM, Kosinski JR, et al. (2012) Butyrate and Propionate Protect against Diet-Induced Obesity and Regulate Gut Hormones via Free Fatty Acid Receptor 3-Independent Mechanisms. PLoS ONE 7(4): e35240. https://doi.org/10.1371/journal.pone.0035240

10.TRANS RESVERATROL + QUERCETIN

Study: “The effects of resveratrol intake on weight loss: a systematic review and meta-analysis of randomized controlled trials”

This study demonstrated the efficacy of resveratrol supplementation on weight loss

This aim of this meta-analysis of randomized controlled trials was conducted to summarize the effect of resveratrol intake on weight loss.

The results showed that resveratrol supplementation significantly decreased body weight, body mass index (BMI), fat mass, and waist circumference (WC), and significantly increased lean mass. This meta-analysis found no significant effect of resveratrol administration on leptin and adiponectin levels. Resveratrol supplementation significantly decreased body weight in obese patients compared to other diseases, and type-2 diabetes mellitus ones. Overall, the current meta-analysis demonstrated that resveratrol intake significantly reduced weight, BMI, WC, and fat mass, and significantly increased lean mass, but did not affect leptin and adiponectin levels.

REFERENCES
  • Tabrizi R, Tamtaji OR, Lankarani KB, Akbari M, Dadgostar E, Dabbaghmanesh MH, Kolahdooz F, Shamshirian A, Momen-Heravi M, Asemi Z. The effects of resveratrol intake on weight loss: a systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2020;60(3):375-390. doi: 10.1080/10408398.2018.1529654. Epub 2018 Nov 13. PMID: 30421960.

11.LIPOSOMAL VIT C

Study: "Evaluation and clinical comparison studies on liposomal and non-liposomal ascorbic acid (vitamin C) and their enhanced bioavailability"

This study evidenced the enhanced bioavailability of liposomal vitamin C compared to its non-liposomal form.

The objective of this clinical study was to evaluate the oral bioavailability of liposomal vitamin C and non-liposomal vitamin C in healthy adult human subjects.

The results showed that liposomal vitamin C by oral delivery is 1.77 times more bioavailable than non-liposomal vitamin C. The liposomal vitamin C demonstrated higher values of Cmax, AUC0-t and AUC0-∞ related to non-liposomal vitamin C due to liposomal encapsulation. No adverse events were reported. It could be concluded that liposomal encapsulated ascorbic acid (vitamin C) shows well-organized morphological pattern, uniform particle size and highly efficient, which leads to enhanced bioavailability.

REFERENCES
  • Gopi, S., & Balakrishnan, P. (2021). Evaluation and clinical comparison studies on liposomal and non-liposomal ascorbic acid (vitamin C) and their enhanced bioavailability. Journal of Liposome Research, 31(4), 356-364.

12.W-BALANCE

Study: "Efficacy of black cohosh (Cimicifuga racemosa L.) in treating early symptoms of menopause: a randomized clinical trial".

This study evidenced that black cohosh reduced the total Greene Climacteric Scale (GCS) score and all GCS subscale scores (vasomotor, psychiatric, physical and sexual symptoms) during 4 and 8 weeks of treatment.

This clinical trial aims to evaluate the efficacy of Black cohosh (Cimicifuga racemosa L.) in treating early menopausal symptoms.

The results showed that the GCS total score (primary outcome) in the treatment group was significantly lower than that in the control group at both week 4 and week 8. The treatment group showed significantly more improvement than the control group in all GCS subscale scores (vasomotor, psychiatric, physical, and sexual symptoms; secondary outcomes). The differences between the treatment and control groups at week 8 were significantly higher (P < 0.001) than those at week 4 in terms of the total scores and the vasomotor and psychiatric subscale scores. No side effects were reported and there was no loss to follow-up during the 8 weeks of treatment.

REFERENCES
  • Mohammad-Alizadeh-Charandabi, S., Shahnazi, M., Nahaee, J., & Bayatipayan, S. (2013). Efficacy of black cohosh (Cimicifuga racemosa L.) in treating early symptoms of menopause: a randomized clinical trial. Medicina china, 8(1), 20.