Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through C-quality evidence.

Class
Qualifying studies
Minimum requirements
A
Systematic review or meta-analysis of human trials
 
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study

Blood sugar dysregulation is a common problem in the United States with more than 29 million people having diabetes, and 86 million people having prediabetes. (16) Type 1 diabetes is due to an autoimmune condition that attacks pancreas beta cells and requires insulin to be managed. Type 2 diabetes mellitus (T2DM) is due to a combination of insulin resistance and insufficiency resulting in high blood glucose levels. (5) Prediabetes describes people with high or poorly controlled blood glucose levels, but not at the point of having type 2 diabetes. (16) When looking at the breakdown between type 1 and type 2 diabetes, type 2 is more prevalent with a study from 2018 citing between 90.4% to 92.1% of diabetes cases to be type 2. 

Dysfunctional blood glucose levels impact other aspects of health as well. People with type 2 diabetes have higher risk for vision loss, heart disease, stroke, kidney failure, circulatory issues, and decreased life expectancy. (16) Additionally, of those with prediabetes, 15-30% progress into type 2 diabetes within five years. (16) Ameliorating blood glucose dysregulation helps to prevent progression and the need for insulin dependence. 

The protocol below presents ingredients based on current research findings that might help regulate blood sugar.

Berberine

500 mg, three times per day, minimum 12 weeks (7) 

  • Meta-analysis of patients with T2DM given berberine exhibited better reduction in fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and HbA1c levels compared to control; additionally, treatment was found to be more effective when combined with hypoglycemic medication or when given for less than 90 days with a dose less than 2 grams per day (13)
  • Meta-analysis of 27 randomized controlled trials found berberine combined with hypoglycemics was more effective than hypoglycemic medications alone, and as equally effective as hypoglycemics when used for T2DM, hyperlipidemia and/or hypertension (12)
  • Systematic review and meta-analysis of 14 randomized trials found berberine combined with lifestyle alterations to be more effective than lifestyle alterations alone; furthermore, berberine enhanced performance of hypoglycemic drugs (7)
  • T2DM patients with dyslipidemia given one gram per day of berberine decreased FPG and postload plasma glucose, as well as improved lipid profile demonstrated by decreases in triglycerides, total cholesterol and LDL compared to placebo (27)
Berberine in the Fullscript catalog

Chromium picolinate

500 µg, two times per day, minimum four weeks (4) 

  • Current literature confirms a minor reduction in blood glucose when supplemented consistently for four weeks or longer (4) 
  • Chromium supplements should be taken with a carbohydrate-containing meal (8)  
  • Meta-analysis of 13 trials found chromium picolinate supplementation to help with glycemic control in diabetics shown by improvements in FPG and cholesterol (23)
  • When given 600 mcg per day of chromium picolinate, patients with T2DM experienced improved glycemic control demonstrated by a decrease in fasting glucose concentration by -31.0 mg/dL compared to -14.0 mg/dL in control group (20)
  • When combined with sulfonylurea, chromium picolinate improved anthropometric markers for body weight, body fat percentage and abdominal fat; additionally, insulin sensitivity improved compared to placebo (15)
  • 63% of T2DM patients responded to chromium picolinate treatment with improved insulin sensitivity compared to 30% in placebo (25)
Chromium picolinate in the Fullscript catalog

Cinnamon

120-360 mg, total per day, minimum 3 months (14)

  • Systematic review and meta-analysis of 18 studies found cinnamon to be effective in improving glucose as shown by a decrease fasting blood sugar by -19.26 mg/dL compared to placebo (17)
  • Meta-analysis of 16 randomized controlled trials found cinnamon supplementation to decreased FBG and improve HOMA-IR in patients with T2DM and pre-diabetes (6)
  • 500 mg of cinnamon bark given twice per day improved BMI, body fat, visceral fat, glycemic control, and lipid profile in patients with T2DM; more pronounced benefits were found in patients with higher baseline BMI (26)
  • When comparing low dose (120 mg/d), high dose(360 mg/d), and placebo, cinnamon supplementation improved hemoglobic H(1c) and FBG in both low and high dose compared to placebo (14)
  • Systematic review and meta-analysis of 10 randomized controlled trials found cinnamon to decrease levels of fasting plasma glucose and improve cholesterol levels when supplementing doses from 120 mg/day to 6 mg/day for 4 to 18 weeks (3) 
Cinnamon in the Fullscript catalog

Psyllium husk

5 g, three times per day, minimum 6 weeks (21)

  • In diabetic patients, demonstrated minor to moderate reduction in blood glucose levels (24) 
  • 15 g daily is a minimum dose and can be titrated up gradually to patient tolerance with no current literature pointing towards an increased benefit of using more than 15 g daily  (22) 
  • Meta-analysis of 35 randomized controlled trials found psyllium to be efficacious lifestyle treatment of patients with T2DM; additionally patients with less glycemic control benefited the most significantly (9)
  • Improved constipation, body weight, glucose and lipid in patients with type 2 diabetes and chronic constipation with (BMI) 20-47 kg/m2 (18) 
  • Insulin sensitivity improved as demonstrated by decrease in FBS, HbA1c, insulin level, C-peptide, HOMA-IR and HOMA-β % compared to control (1)
Psyllium husk in the Fullscript catalog

Probiotics

Probiotic with mixed strains, as directed on bottle (2)(10)

  • Meta-analysis of 8 randomized controlled trials found probiotics to be effective in improving metabolic control in patients with T2DM, as shown by a reduction in HbA1c and HOMA-IR  (10)
  • When given a mixed probiotic of seven strains of Lactobacillus, Bifidobacterium and Streptococcus for five weeks, patients with T2DM experienced decreased FPG and increased HDL-C (21)
  • Patients with T2DM experienced decreased HOMA-IR and HbA1c by 0.39% and improved insulin resistance when given a mixed probiotic for 8 weeks (11)
  • Systematic review and meta-analysis of 13 clinical trials found probiotics to decrease fasting blood glucose and A1c (2)
  • A 12-week parallel, double-blind, placebo-controlled trial including 76 patients with T2DM found that supplementation with C. beijerinckii, C. butyricum, B. infantis, A. muciniphila, and A. hallii significantly improved glucose total area under the curve (-36.1 mg/dL/180 min), HbA1c (-0.6%), and glucose incremental-AUC (-28.6 mg/dL/180 min) (20)
Probiotics in the Fullscript catalog

Disclaimer

The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

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References
  1. Abutair, A. S., Naser, I. A., & Hamed, A. T. (2016). Soluble fibers from psyllium improve glycemic response and body weight among diabetes type 2 patients (randomized control trial). Nutrition Journal, 15(1), 86. https://pubmed.ncbi.nlm.nih.gov/27733151/ (C)
  2. Akbari, V., & Hendijani, F. (2016). Effects of probiotic supplementation in patients with type 2 diabetes: systematic review and meta-analysis. Nutrition Reviews, 74(12), 774–784. https://pubmed.ncbi.nlm.nih.gov/27864537/ (A)
  3. Allen, R. W., Schwartzman, E., Baker, W. L., Coleman, C. I., & Phung, O. J. (2013). Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Annals of Family Medicine, 11(5), 452–459. https://pubmed.ncbi.nlm.nih.gov/24019277/ (A)
  4. Anderson, R. A., Cheng, N., Bryden, N. A., Polansky, M. M., Cheng, N., Chi, J., & Feng, J. (1997a). Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes, 46(11), 1786–1791. https://pubmed.ncbi.nlm.nih.gov/9356027/ (C) 
  5. Bullard, K. M., Cowie, C. C., Lessem, S. E., Saydah, S. H., Menke, A., Geiss, L. S., Orchard, T. J., Rolka, D. B., & Imperatore, G. (2018). Prevalence of Diagnosed Diabetes in Adults by Diabetes Type – United States, 2016. MMWR. Morbidity and Mortality Weekly Report, 67(12), 359–361. https://pubmed.ncbi.nlm.nih.gov/29596402/ (F)
  6. Deyno, S., Eneyew, K., Seyfe, S., Tuyiringire, N., Peter, E. L., Muluye, R. A., Tolo, C. U., & Ogwang, P. E. (2019). Efficacy and safety of cinnamon in type 2 diabetes mellitus and pre-diabetes patients: A meta-analysis and meta-regression. Diabetes Research and Clinical Practice, 156, 107815. https://pubmed.ncbi.nlm.nih.gov/31425768/ (A)
  7. Dong, H., Wang, N., Zhao, L., & Lu, F. (2012). Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evidence-Based Complementary and Alternative Medicine: eCAM, 2012, 591654. https://pubmed.ncbi.nlm.nih.gov/23118793/ (A)
  8. Frauchiger, M. T., Wenk, C., & Colombani, P. C. (2004). Effects of acute chromium supplementation on postprandial metabolism in healthy young men. Journal of the American College of Nutrition, 23(4), 351–357. https://pubmed.ncbi.nlm.nih.gov/15310739/ (C)
  9. Gibb, R. D., McRorie, J. W., Jr, Russell, D. A., Hasselblad, V., & D’Alessio, D. A. (2015). Psyllium fiber improves glycemic control proportional to loss of glycemic control: a meta-analysis of data in euglycemic subjects, patients at risk of type 2 diabetes mellitus, and patients being treated for type 2 diabetes mellitus. The American Journal of Clinical Nutrition, 102(6), 1604–1614. https://pubmed.ncbi.nlm.nih.gov/26561625/ (A)
  10. Kasińska, M. A., & Drzewoski, J. (2015). Effectiveness of probiotics in type 2 diabetes: a meta-analysis. Polskie Archiwum Medycyny Wewnetrznej, 125(11), 803–813. https://pubmed.ncbi.nlm.nih.gov/26431318/ (A)
  11. Kobyliak, N., Falalyeyeva, T., Mykhalchyshyn, G., Kyriienko, D., & Komissarenko, I. (2018). Effect of alive probiotic on insulin resistance in type 2 diabetes patients: Randomized clinical trial. Diabetes & Metabolic Syndrome, 12(5), 617–624. https://pubmed.ncbi.nlm.nih.gov/29661605/ (B)
  12. Lan, J., Zhao, Y., Dong, F., Yan, Z., Zheng, W., Fan, J., & Sun, G. (2015). Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. Journal of Ethnopharmacology, 161, 69–81. https://pubmed.ncbi.nlm.nih.gov/25498346/ (A)
  13. Liang, Y., Xu, X., Yin, M., Zhang, Y., Huang, L., Chen, R., & Ni, J. (2019). Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis. Endocrine Journal, 66(1), 51–63. https://pubmed.ncbi.nlm.nih.gov/30393248/ (A)
  14. Lu, T., Sheng, H., Wu, J., Cheng, Y., Zhu, J., & Chen, Y. (2012). Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes. Nutrition Research , 32(6), 408–412. https://pubmed.ncbi.nlm.nih.gov/22749176/ (B)
  15. Martin, J., Wang, Z. Q., Zhang, X. H., Wachtel, D., Volaufova, J., Matthews, D. E., & Cefalu, W. T. (2006). Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care, 29(8), 1826–1832. https://pubmed.ncbi.nlm.nih.gov/16873787/ (C)
  16. https://www.cdc.gov/media/releases/2014/p0610-diabetes-report.html#:~:text=People%20with%20diabetes%20often%20use,for%20Disease%20Control%20and%20Prevention.n (F) More than 29 million Americans have diabetes; 1 in 4 doesn’t know. (2019, February 4). 
  17. Namazi, N., Khodamoradi, K., Khamechi, S. P., Heshmati, J., Ayati, M. H., & Larijani, B. (2019). The impact of cinnamon on anthropometric indices and glycemic status in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials. Complementary Therapies in Medicine, 43, 92–101. https://pubmed.ncbi.nlm.nih.gov/30935562/ (A)
  18. Noureddin, S., Mohsen, J., & Payman, A. (2018). Effects of psyllium vs. placebo on constipation, weight, glycemia, and lipids: A randomized trial in patients with type 2 diabetes and chronic constipation. Complementary Therapies in Medicine, 40, 1–7. https://pubmed.ncbi.nlm.nih.gov/30219432/ (C)
  19. Paiva, A. N., Lima, J. G. de, Medeiros, A. C. Q. de, Figueiredo, H. A. O., Andrade, R. L. de, Ururahy, M. A. G., Rezende, A. A., Brandão-Neto, J., & Almeida, M. das G. (2015). Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. Journal of Trace Elements in Medicine and Biology: Organ of the Society for Minerals and Trace Elements , 32, 66–72. https://pubmed.ncbi.nlm.nih.gov/26302914/ (C)
  20. Perraudeau, F., McMurdie, P., Bullard, J., Cheng, A., Cutcliffe, C., Deo, A., Eid, J., Gines, J., Iyer, M., Justice, N., Loo, W. T., Nemchek, M., Schicklberger, M., Souza, M., Stoneburner, B., Tyagi, S., & Kolterman, O. (2020). Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Research & Care, 8(1). https://doi.org/10.1136/bmjdrc-2020-001319 (C)
  21. Razmpoosh, E., Javadi, A., Ejtahed, H. S., Mirmiran, P., Javadi, M., & Yousefinejad, A. (2019). The effect of probiotic supplementation on glycemic control and lipid profile in patients with type 2 diabetes: A randomized placebo controlled trial. Diabetes & Metabolic Syndrome, 13(1), 175–182. https://pubmed.ncbi.nlm.nih.gov/30641692/ (B)
  22. Rodríguez-Morán, M., Guerrero-Romero, F., & Lazcano-Burciaga, G. (1998). Lipid- and glucose-lowering efficacy of Plantago Psyllium in type II diabetes. Journal of Diabetes and Its Complications, 12(5), 273–278. https://pubmed.ncbi.nlm.nih.gov/9747644/ (B)
  23. San Mauro-Martin, I., Ruiz-León, A. M., Camina-Martín, M. A., Garicano-Vilar, E., Collado-Yurrita, L., Mateo-Silleras, B. de, & Redondo Del Río, M. D. P. (2016). [Chromium supplementation in patients with type 2 diabetes and high risk of type 2 diabetes: a meta-analysis of randomized controlled trials]. Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral, 33(1), 27. https://pubmed.ncbi.nlm.nih.gov/27019254/ (A)
  24. Sierra, M., García, J. J., Fernández, N., Diez, M. J., & Calle, A. P. (2002). Therapeutic effects of psyllium in type 2 diabetic patients. European Journal of Clinical Nutrition, 56(9), 830–842. https://pubmed.ncbi.nlm.nih.gov/12209371/ (C)
  25. Wang, Z. Q., Qin, J., Martin, J., Zhang, X. H., Sereda, O., Anderson, R. A., Pinsonat, P., & Cefalu, W. T. (2007). Phenotype of subjects with type 2 diabetes mellitus may determine clinical response to chromium supplementation. Metabolism: Clinical and Experimental, 56(12), 1652–1655. https://pubmed.ncbi.nlm.nih.gov/17998017/ (B)
  26. Zare, R., Nadjarzadeh, A., Zarshenas, M. M., Shams, M., & Heydari, M. (2019). Efficacy of cinnamon in patients with type II diabetes mellitus: A randomized controlled clinical trial. Clinical Nutrition , 38(2), 549–556. https://pubmed.ncbi.nlm.nih.gov/29605574/ (B)
  27. Zhang, Y., Li, X., Zou, D., Liu, W., Yang, J., Zhu, N., Huo, L., Wang, M., Hong, J., Wu, P., Ren, G., & Ning, G. (2008). Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. The Journal of Clinical Endocrinology and Metabolism, 93(7), 2559–2565. https://pubmed.ncbi.nlm.nih.gov/18397984/ (C)