plant based medicines

calcium fructoborate

This post started with mining references from a Hungarian boron review. Borate and hormones, we know anecdotally that something is going on. After writing this post, what is the image to summarize everything? We really know NOTHING. The featured image is of borate binding to a serine rich pocket of porcine trypsin. The PubMed abstract associated with this entry suggests that the study was designed to test the hypothesis that learning about a low affinity site on porcine trypsin will help us predict other borate binding sites on serine rich regions of other proteins. Most of the work on boron and predicted hormonal effects comes from Romania and their product calcium fructoborate, which they argue is exactly the same as what is found in plants. Perhaps the fructose part is directing deposition of the borate to specific serine rich surface pockets.

A hodgepodge of comments on calcium fructoborate [1-6]

The first Romanian review [1] did not have much useful to say. An Iranian study postulated that liposomal calcium fructoborate would have an effect on a breast cancer cell line. [2]

A Romanian review contained one paragraph comments on three clinical trials on calcium fuctoborate for cardiovascular diseases. [3] B cross-links glycoproteins in cell membranes. Subsequently, the most probable action mechanism of CF may be the chemical bonding of fructoborate to specific cytokines glycoproteic receptors at the surface of the cellular membrane. This may be happening since the fructoborate pKa 4.16 is lower than the cellular pH 7.4, compared with the boric acid whose pKa 9.24 is higher than the cellular pH. Consequently, fructoborate has a better interaction capacity with glycoproteins versus that of the boric acid/borate. Furthermore, the free boric acid generated by hydrolysis of the fructoborate complex was recently shown to crystallize in the hexagonal system rather than in the triclinic system as compared to the regular boric acid. [3] Romanians continue to publish reviews on calcium fructoborate [4,5] We learn that CFB is patented. [5]

Using cellular modelsborate was found to inhibit adipogenesis via CCAAT-enhancer-binding protein α and peroxisome proliferator-activated receptor γ, by regulating critical growth factors and the β-catenin, AKT, and extracellular signal-regulated kinase signaling pathways. [6]

Ca2+ fructo borate and changes in lipid profiles [7]

This was yet another Romanian study.

Male and female participants were considered for inclusion:

  • 40 and 60 years
  • (BMI) between 24 and 27 kg/m2
  • normal blood pressure or minor hypertension (<140/80–90 mmHg),
  • blood CRP >3 mg/L, LDL >130 mg/dL
  • elevated triglycerides (>200 mg/dL), HDL <40 mg/dL
  • fasting glucose <100 mg/dL.

Participants were instructed to fast for at least 12 h prior to the beginning of the trial. Supplements were distributed to the participants after initial blood collection on the first day of the trial. The test formulation was CFB, a patented commercially available dietary supplement

  • Group A (CFB-1) received 112 mg/day of CFB given as a 56-mg dose twice daily, which is the equivalent to 3.0 mg boron/day.
  • Group C (CFB-2) received 56 mg/day CFB as a 28-mg dose twice daily, the equivalent to 1.5 mg boron/day.
  • Group B, the placebo arm, received 80 mg/day fructose given as a 40-mg dose twice daily; this dosage is equal to the amount of fructose present in 112 mg CFB. T
Group AGroup BGroup Cp value between-groupsaPost hoc comparisonAdjusted p valueb
Total cholesterol95.1 ± 5.899.5 ± 5.793.4 ± 5.1<0.001***B-A0.027*
95.4 (84.6–106.9)99.2 (82.0–15.3)95.2 (82.6–101.8)C-A0.667
HDL-Chol.105.8 ± 20.9100.5 ± 8.6104.6 ± 6.70.207
103.9 (62.1–171.8)101.0 (76.5–18.7)104.7 (89.0–118.5)
LDL-Chol.90.2 ± 7.798.6 ± 7.190.6 ± 10.3<0.001***B-A<0.001***
91.4 (75.3–101.0)99.2 (76.4–111.3)96.4 (70.0–102.7)C-A0.816
Triglycerides90.9 ± 10.499.0 ± 11.191.2 ± 7.1<0.001***B-A0.007**
91.5 (72.4–113.3)98.8 (73.0–129.3)93.4 (78.7–99.7)C-A0.96
A sampling of Table 3. More is available in the publication [7] Changes from baseline (% change) for each parameter are summarized as mean ± SD or median (range). Group A, CFB-1 (112 mg/day CFB); group B, placebo; group C, CFB-2 (56 mg/day CFB)
a p values are from Kruskal-Wallis one-way ANOVA testb Adjusted p values are from Tukey’s HSD test Table 3 Summary of changes from baseline between groups and pairwise multiple comparisons for each parameter***p < 0.001; **p < 0.01; *p < 0.05

Ca2+ fructoborate and rheumatoid arthritis [8,9]

This study came out of Baghdad Iraq. Of the 80 that started the study, 72 completed the study. Patients consumed the products in a single daily dose after a meal.

  • 220 mg/day CFB, 55 mg/day NTB in capsule dosage form (equivalent to 6 mg elemental Boron)
  • 55mg sodium tetra borate (NTB) per day equivalent to 6m elemental boron…
  • placebo formula once daily.

The authors claimed that both boron compounds decreased serum TNFα and that CFB is slightly better. [8] Yet another Romanian review speculates that this anti-inflammatory effect on cytokines is due to decreasing superoxide content. [9]

Ca2+ fructoborate + resveratrol and angina [10]

This study came out of Romania. Nearly all of these subjects had a history of hypertension, were on some sort of medication for the hypertension. All three groups were in their mid 60s plus or minus five years. Close to half in each group had had a myocardial infarction. All had been diagnosed with angina pectoris (CCS classes II–IV), pain that is caused by reduced blood flow to the heart. All patients continued to receive their normal care.

  • Group 1 20 mg/d trans-resveratrol
  • Group 2 20 mg/d (trans-resveratrol 10.0 mg) + CFB 112 mg/d (boron 3.0 mg/d)
  • Group 3  CFB 112 mg/d (boron 3.0 mg/d)
  • control group received only their usual medical care and treatment.

Table 2. Changes in hs-CRP and NT-proBNP

Empty CellInclusionMonth 1Month 2P
hs-CRP (mg/L)
 Group 16.9 ± 2.55.7 ± 1.9 (−17.3%)5.2 ± 1.7 (−24.6%)0.03
 Group 26.6 ± 2.66.2 ± 2.5 (−6%)4.6 ± 1.8 (−30.3%)0.02
 Group 36.8 ± 1.95.3 ± 2.5 (−22%)4.1 ± 1.5 (−39.7%)0.005
 Control6.6 ± 2.46.2 ± 2.1 (−6%)5.9 ± 2.6 (−10.6%)0.04
NT-proBNP (pg/mL)
 Group 1674 ± 192552 ± 232 (−18.1%)271 ± 137 (−59.7%)0.02
 Group 2662 ± 238498 ± 147 (−24.7%)228 ± 84 (−65.5%)0.01
 Group 3684 ± 151531 ± 165 (−22.3%)324 ± 102 (−52.6%)0.03
 Control671 ± 218582 ± 197 (−13.2%)514 ± 207 (−23.3%)0.04

hs-CRP, high-sensitivity C-reactive protein; NT-proBNP, N-terminal prohormone of brain natriuretic peptide Data are presented as mean ± SD (percentage of differences from baseline) * Statistical significance from baseline, computed at the end of trial (Student t test).

Not shown are changes in the cholesterol profile and such as that. hs-CRP and pro-BNP showed significant changes in a relatively short time (2 mo) in all groups. The authors claim more significant changes in the CFB groups.

Ca2+ fructoborate for osteoarthritis [11]

This study also came out of Romania. In this study of men and women between 40 and 85 years old osteoarthritis was defined as “deterioration and abrasion of the articular cartilage (joint space narrowing) or by the formation of a new bone (osteophytes) at the knee joint surface (medial tibiofemoral, lateral tibiofemoral, or patellofemoral).”

  • Group 1: 28.5 mg CF (1.5 mg boron/day) twice per day
  • Group 2: 56.5 mg CF (3.0 mg boron/day) twice per day
  • Group 3: 113 mg CF (6.0 mg boron/day) twice per day
  • Placebo group: 120 mg placebo twice per day. Placebo material was based only on fructose

Table 3 has been edited to only include the statistical significance and percent changes from baseline rows.

Variable (measurement)Patients groups
PlaceboGroup 1Group 2Group 3
Triglycerides (p)a0.367670.422010.092140.30010
% change from baseline7.5−6.5−22.87−2.1
Cholesterol (p)a0.163360.013780.148750.27139
% change from baseline5.4−9.01−2.6−1.92
HDL cholesterol (p)a0.193200.158950.387990.11081
% change from baseline8.51−3.772.045.45
LDL cholesterol (p)a0.105290.005550.423150.15522
% change from baseline6.66−12.190.69−2.85
Note that group 3 has has the highest concentration of CFB The curious thing is that the low dose of CFB gave the only significant changes and that these changes were the largest and negative.

The erythrocyte sedimentation rate is increased during inflammation and autoimmune disorders. One explanation is that fibrinogen causes the red blood cells to clump together. Fibrinogen is the glycoprotein produced in the liver that is converted to fibrin by the action of thrombin. C reactive protein is secreted by the liver in response to IL=6

parameterPatients groups
PlaceboGroup 1Group 2Group 3
Erythrocyte sedimentation rate (p)a0.000580.028930.376390.07280
% change from baseline36.36−10.25−11.9−8.5
fibrinogen (p)a0.045530.000580.358220.36227
% change from baseline4.10−13.73−2.05−4.18
C reactive peptide (p)a0.005400.024530.069640.11227
% change from baseline5.47−60.25−26.66−17.54
data from ref [11] all but the % change and p significance values have been edited out for simplicity. Note that the only significant changes are in the placebo group and the lower concentration of CFB. Also note that the changes go in opposite directions!


  1. Hunter J.M., Nemzer B.V., Rangavajla N., Biţă A., Rogoveanu O.C., Neamţu J., Scorei I.R., Bejenaru L.E., Rău G., Bejenaru C., et al. The fructoborates: Part of a family of naturally occurring sugar–borate complexes—Biochemistry, physiology, and impact on human health: A review. Biol. Trace Elem. Res. 2019;188:11–25. doi: 10.1007/s12011-018-1550-4. [PMC free article]
  2. Pirouz F., Najafpour G., Jahanshahi M., Sharifzadeh Baei M. Biodistribution of calcium fructoborate as a targeting agent for boron neutron capture therapy in an experimental model of MDA-MB-231 breast cancer cells. Biocatal. Agric. Biotechnol. 2019;22:101389. doi: 10.1016/j.bcab.2019.101389. [CrossRef]
  3. Mogoşanu G.D., Biţă A., Bejenaru L.E., Bejenaru C., Croitoru O., Rău G., Rogoveanu O.C., Florescu D.N., Neamţu J., Scorei I.D., et al. Calcium fructoborate for bone and cardiovascular health. Biol. Trace Elem. Res. 2016;172:277–281. doi: 10.1007/s12011-015-0590-2. [PMC free article]
  4. Miljkovic D., Scorei R.I., Cimpoiaşu V.M., Scorei I.D. Calcium fructoborate: Plant-based dietary boron for human nutrition. J. Diet. Suppl. 2009;6:211–226. doi: 10.1080/19390210903070772. [PubMed] [CrossRef]
  5. Scorei I.D., Scorei R.I. Calcium fructoborate helps control inflammation associated with diminished bone health. Biol. Trace Elem. Res. 2013;155:315–321. doi: 10.1007/s12011-013-9800-y. [PubMed] [CrossRef]
  6. Doğan A., Demirci S., Apdik H., Bayrak O.F., Gulluoglu S., Tuysuz E.C., Gusev O., Rizvanov A.A., Nikerel E., Şahin F. A new hope for obesity management: Boron inhibits adipogenesis in progenitor cells through the Wnt/β-catenin pathway. Metabolism. 2017;69:130–142. doi: 10.1016/j.metabol.2017.01.021. [PubMed] [CrossRef]
  7. Rogoveanu O.C., Mogoşanu G.D., Bejenaru C., Bejenaru L.E., Croitoru O., Neamţu J., Pietrzkowski Z., Reyes-Izquierdo T., Biţă A., Scorei I.D., et al. Effects of calcium fructoborate on levels of C-reactive protein, total cholesterol, low-density lipoprotein, triglycerides, IL-1β, IL-6, and MCP-1: A double-blind, placebo-controlled clinical study. Biol. Trace Elem. Res. 2015;163:124–131. doi: 10.1007/s12011-014-0155-9. [PMC free article]
  8. Hussain S.A., Abood S.J., Gorial F.I. The adjuvant use of calcium fructoborate and borax with etanercept in patients with rheumatoid arthritis: Pilot study. J. Intercult. Ethnopharmacol. 2016;6:58–64. doi: 10.5455/jice.20161204021549. [PMC free article] [PubMed] [CrossRef]
  9. Scorei R.I., Rotaru P. Calcium fructoborate—Potential anti-inflammatory agent. Biol. Trace Elem. Res. 2011;143:1223–1238. doi: 10.1007/s12011-011-8972-6. [PubMed]
  10. Militaru C., Donoiu I., Craciun A., Scorei I.D., Bulearca A.M., Scorei R.I. Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: Effects on lipid profiles, inflammation markers, and quality of life. Nutrition. 2013;29:178–183. doi: 10.1016/j.nut.2012.07.006. [PubMed] [CrossRef]
  11. Scorei R., Mitrut P., Petrisor I., Scorei I. A double-blind, placebo-controlled pilot study to evaluate the effect of calcium fructoborate on systemic inflammation and dyslipidemia markers for middle-aged people with primary osteoarthritis. Biol. Trace Elem. Res. 2011;144:253–263. doi: 10.1007/s12011-011-9083-0. [PMC free article]

Leave a Reply