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Calcium fructoborate: a new mineral complex with anti-inflammatory action.

The role of inflammation is well established as a major contributing factor in chronic illness and aging. Consequently, the management of inflammatory process has become an important goal in both integrative and standard practice. Clinicians in functional and longevity medicine address this issue with specialized lab testing, diet, and a range of supplementation strategies. Here we review a new, but well researched natural supplement, calcium fructoborate, an agreeably tolerated, easily absorbed, moderately-priced mineral compound affecting a number of fundamental processes integral to human health, including the reduction of inflammation.

Calcium Fructoborate (CF). CF is a boron-based mineral complex composed of calcium, fructose, and boron in a patented formulation, with more than a dozen research studies showing the potential to affect functional dynamics in the body, including:

* Inflammation--reduces CRP levels consistently in all studies by approximately 40%

* Markers of cardio risk--lowers TChol, LDL, and IL-6, and raises HDL

* Incidence of angina--50% reduction in angina episodes in a clinical trial

* Important indicator of congestive heart failure--reduces N-terminal prohormone of brain natriuretic peptide, a marker of left ventricle function

* Joint health and osteoarthritis--reduces markers of inflammation such as CRP, IL-6, and IL-1, and users report improved comfort and flexibility

* Bone health, including osteoporosis--reduction of inflammatory markers and bone resorption

* Possible cancer prevention--in vitro studies show enhanced apoptosis of cancer cell lines and moderation of oncogene expression

Why Boron?

Boron is a nutrient essential for human health. Epidemiological studies of population health and boron content in soil show higher rates of arthritis in areas with low-boron soil levels. These findings have stimulated research on the biochemistry of boron in living systems and the effects of various boron compounds in different types of experimental situations. (1) This has led to the identification and study of calcium fructoborate, a naturally occurring boron compound present in small amounts in many fruits, vegetables, legumes, herbs, and wine. CF is readily synthesized, well-absorbed, and non-toxic, and has demonstrated beneficial impact on several metabolic processes that underlie osteoarthritis, osteoporosis, and other chronic conditions.

Of special interest is the finding that CF reduces some biochemical markers of inflammation such as CRP and IL6, but does not reduce levels of another key indicator of inflammation, COX-2. Recent research has highlighted the importance of COX-2 in the natural process of inflammatory resolution and the problems caused by blocking this important enzyme.

The Dark Side of Anti-inflammatories: The COX-2 Story

A vastly more detailed understanding of the natural process of inflammation resolution has emerged from a series of meticulous studies on inflammation by Charles Serhan, PhD and his team at Harvard. (2,3) While an in-depth review of their findings is beyond the scope of this article, a key take-home is the realization that we have been looking at only half of the inflammation story. Studies from this Harvard team demonstrate the way in which NSAIDs and certain natural remedies actually interfere with healing. The use of calcium fructoborate avoids this dilemma.

The Two Phases of Inflammation. The initial phase of inflammation is defined by release of numerous cytokines such as CRP, IL-6, and COX-2. Reducing the levels of these key inflammatory cytokines has been the target of anti-inflammatory drugs and certain botanical products found to provide pain relief. Although this may seem logical, it is here that the problem begins.

Serhan's group examined the underlying processes by which episodes of inflammation are resolved in a healthy, well-nourished body. An extensive range of experiments identified new classes of substances termed resolvins and protectins that occur naturally in inflammatory states and set the stage for the body, tissues, and organs to heal. Researchers described inflammation as a process with two general phases: initiation and resolution. Initiation occurs after an insult or attack on the body such as infection, an injury, or a metabolic imbalance. At this point, inflammation is initiated, and inflammatory cytokine levels are elevated. This research found that the initial process of inflammation lays the foundation for a second phase of healing and ultimately for resolution of damage to the tissue. The second or resolution phase begins when the elevated levels of inflammatory cytokines trigger the release of resolvins and protectins, which direct the immune system to alter its function. In this second phase, the system destroys any infectious material, cleans up debris, and triggers the healing of tissues and organs.

The Catch-22. The high level of cytokines in the initiation phase, particularly COX-2, is what triggers the resolution phase. However, current anti-inflammatory drugs and certain supplements are designed to reduce this key cytokine. The production of resolvins and protectins is required for the natural progression of the resolution phase. Consequently, blocking COX-2 impedes healing, contributing to chronic inflammation.

This dynamic helps to explain situations such as the Vioxx disaster. Vioxx was a powerful, selective COX-2 inhibitory drug. It was very successful commercially because it caused fewer stomach problems than any previous NSAID and reduced pain effectively. However, this potent drug, particularly at higher doses, blocked COX-2 activity which impeded the body's natural repair processes, resulting in damage to the heart, circulation, and kidneys. It is estimated that between 90,000 and 300,000 heart attacks can be attributed to Vioxx, many of them fatal. The final cost to the drug company was more than $4 billion.

Calcium Fructoborate Research

The discovery of boron carbohydrate complexes with a range of anti-inflammatory and anti-oxidant effects has led to the reassessment of boron's therapeutic applications. A natural sugar-borate ester, CF is a source of soluble boron, biologically active at the intracellular level as free boric acid and at the extracellular level as fructose borate, diester, and monoester. CF has demonstrated beneficial effects on oxidative metabolism and cell apoptosis. (4) Clinical effects demonstrated in the research include reductions in CRP levels by 30% to 40% and the stimulation of superoxide dismutase activity by more than 70%. (5)

Cardiovascular Health. There are two studies of real significance in this area. The research of greatest clinical relevance was a randomized, double-blind trial that tracked four groups of middle age men (n = 116) with stable angina pain. (6) In addition to usual care and treatment provided to all patients, those in group 1 received resveratrol, group 2 received resveratrol plus calcium fructoborate, and group 3 received calcium fructoborate alone. Outcomes included a marker of left ventricle function (N-terminal prohormone), CRP, lipids, and the number of angina attacks per week.

CF and resveratrol were provided in combination, because resveratrol is rapidly degraded in the Gl tract. CF protects resveratrol from deterioration in the gut, supporting higher levels of resveratrol absorption and longer effective time in the body. Additionally, as this study demonstrated, there is a synergistic effect of taking these two supplements together. The most significant outcome of this clinical trial was a 49.8% reduction in angina episodes after 60 days.

The second study of relevance to cardiovascular issues is research evaluating the effects of CF on blood parameters and proinflammatory cytokines in healthy subjects. This randomized, double-blinded, placebo-controlled trial tracked responses after 30 days of a placebo or CF at a dose of 56 mg/ day or 112 mg/day. (7)

Parameters tested included C-reactive protein, homocysteine, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, interleukin lb, interleukin 6, and monocyte chemoattractant protein-1. The most noteworthy results were achieved with 30 days of CF supplementation at 112 mg, which reduced C-reactive protein, interleukin lb, and MCP-1 each approximately 30%.

Osteoarthritis. A number of studies have looked at the role of key inflammatory cytokines in osteoarthritis and the effect of CF on cytokine chemistry:

* Knee pain. A double-blind, cross-over study of 60 people with osteoarthritic knee pain tracked patients for 15 days. CF showed consistent reduction in inflammatory markers and improved comfort and flexibility. (8)

* CRP and calcitrol. In another double-blind, cross-over study involving 10 subjects for 15 days, CRP levels dropped 37%. Subjects also showed a 19% increase in calcitrol, the active form of vitamin D3, and this was without any increase in the amount of vitamin D3 supplementation. (9)

Osteoporosis (OP). Review studies report that CF appears to be useful in preventing and managing OP. (10) The literature indicates that the majority of osteoporosis cases involve bone resorption (osteoclast) that is too rapid relative to bone building (osteoblast). There is clear evidence that inflammation is a significant component of this process. One of the inflammatory compounds found to be central to osteoporosis is termed RANKL (receptor activator of nuclear factor kappa-b ligand). Increases in RANKL directly cause bone resorption. Given the improvement observed in osteoporosis with the use of CF, we can presume that levels of RANKL are simultaneously being reduced.

Cancer Prevention. Boron has been investigated for its impact on cancer, and CF has been specifically evaluated through in vitro research. A study comparing the effects of CF and boric acid found both effective in inhibiting breast cancer cell growth (MDA-MB-231 cell line) in a dose-dependent manner. However, only CF increased and normalized apoptotic activity. Treatment with calcium fructoborate (but not with boric acid) was found to reduce p53 and bd-2 proteins levels, markers that reflect pro-cancer genetic expression. We look forward to seeing more research on this aspect of CF. (11)

Clinical Applications

Systemic inflammation presents a major challenge in the management of chronic conditions such as cardiovascular disease and osteoarthritis in which inflammation interferes with the body's normal repair and regulatory processes. Consequently, the utility of calcium fructoborate in reducing total body inflammation makes it relevant to a broad range of clinical applications. At Lifespan, our experience bears this out.

In the management of chronic conditions, clients may be taking an excellent support protocol of supplements, but not getting the desired results. Lab findings with elevated CRP, IL-6, or other inflammatory markers indicate that systemic inflammation is a primary interfering issue (but possibly not the only factor). Reducing total body inflammation can unencumber the body's natural healing processes, maximizing the benefit of nutritional supplements and facilitating recovery. CF has strong potential application in these common situations.

Functional programs for chronic issues usually rely on specialized lab tests, leaky gut protocols, low antigenic diets, and a number of supplements. Major drawbacks to this approach have been complexity, cost, the need to make substantial lifestyle changes, and the gradual nature of improvement, particularly in conditions that have persisted for years or even decades. Calcium fructoborate appears to be a useful adjunct to the anti-inflammatory tool box of functional nutrition.

Cardiovascular Support

The medical literature identifies elevated CRP levels as a contributor to essentially all aspects of cardiovascular pathology. Outcomes are worse if CRP levels are higher or uncontrolled in resistant hypertension, coronary artery disease, congestive heart failure, atrial fibrillation, and diabetic vascular complications. CF, particularly in conjunction with resveratrol, appears to be a basic adjunct to a functional cardio support program.

In our cardio protocol at Lifespan, we utilized this combination in the nutritional support of a client with congestive heart failure (CHF), following a resveratrol protocol for CHF from the literature. The resveratrol was taken in combination with CF, as in the angina clinical trial. The subjective response in this case was perceived improvement in endurance and in recovery from moderate exercise.


Our most extensive experience in the use of CF has been the provision of nutritional support for arthritis and joint problems. A number of different functional impairments can be at play in this common, but difficult-to-manage problem:

* Bone morphogenic protein. Age-related decreases in bone morphogenic protein (BMP) slow the repair and production of joint tissue in conjunction with increased systemic inflammation. We support BMPs with Ostinol[R] and Chondrinol[R].

* Inflammation. Increased inflammatory cytokines and systemic inflammation appear to block many natural healing processes. Frequently, inflammation must be reduced before other products can work effectively. In our protocols, CF is always combined with connective tissue support products.

* Autoimmunity. In these cases, there are not only high levels of inflammation, but also immune activity targeting the tissues of the body. Given the complexity of these conditions, we utilize testing from Cyrex to focus our programs. Basic products are selected to support T-regulatory activity include glutathione, super oxide dismutase, fish oil, and vitamin D.

* Microcirculation impairment. This refers to blockage of fine capillaries in the vicinity of a painful joint or injury. Constriction of capillary circulation compromises the tissues' ability to function and repair. Products such as Yan's Heng Fa #1[R], Herbal Yuth[R], or lumbrokinase can be employed to support microcirculation.


In support programs for osteoporosis, we combine CF with bone morphogenic proteins (Ostinol[R]). However, we do not find high calcium doses to have substantial impact on osteoporosis. Rather, OP seems to be primarily an issue of inflammation and lack of BMPs.


Calcium fructoborate is a promising new tool for functional nutrition practitioners. This supplement offers a modest price point, convenient dosing, and a broad range of uses in health conditions with an inflammatory component. CF can be effectively integrated in many functional medicine programs, reducing inflammation without disrupting natural inflammatory resolution and healing. Already well-studied, more research is underway that will further determine usefulness in difficult and painful chronic conditions.

Author: Jerry Stine

Jerry Stine is a nutritional consultant and the director of the Lifespan Institute for Functional and Anti-Aging Nutrition, which he founded in 1987 to develop advanced life-extension and performance-enhancement programs. For the past 20 years, he has been an independent nutritional counselor with an active private practice and has served as consultant for several respected vitamin manufacturers. For more information, he can reached by phone at 707-421 2143 or at

Resources: Product Details

Calcium fructoborate is sold under the name FruiteX-B and comes in 120 capsule bottles. Each capsule contains 108 mg of CF. This product is manufactured by FutureceuticalsDirect. com. For consumer sales, see or Contact Lifespan at:

Phone: 707-421-2143

Fax: 707-421-2146


Editorial: Nancy Faass

Nancy Faass, MSW, MPH, is a writer and editor in San Francisco who has worked on more than 45 books for publishers that include Elsevier, Harper, McGraw Hill, New World Library, and others. Director of the Writers' Group for the past 20 years, she works collaboratively with clients to develop articles, Web content, white papers, blogs, manuals, and books and can be reached by emailing or calling 415-922-6234.


(1.) Naghii MR, Mofid M, Asgari AR, Hedayati M, Daneshpour MS. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. J Trace Elem Med Biol. 2011 Jan;25(1):54-8. Epub 2010 Dec 3.

(2.) Colas RA, Shinohara M, Dalli J, Chiang N, Serhan CN. Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue. Am J Physiol Cell Physiol. 2014 Jul l;307(1):C39-54.

(3.) Hsiao HM, Thatcher TH, Colas RA, Serhan CN, Phipps RP, Sime PJ. Resolvin D1 reduces emphysema and chronic inflammation. Am J Pathol. 2015 Dec;185(12):3189-201. Epub 2015 Oct 24.

(4.) Miljkovic D, Scorei Rl, Cimpoia$u VM, Scorei ID. Calcium fructoborate: plant-based dietary boron for human nutrition. J Diet Suppl. 2009;6(3):211-26.

(5.) Scorei R, Ciubar R, lancu C, Mitran V, Cimpean A, lordachescu D. In vitro effects of calcium fructoborate on fMLP-stimulated human neutrophil granulocytes. Biol Trace Elem Res. 2007 Jul;118(1):27-37.

(6.) Militaru C, Donoiu I, Craciun A, Scorei ID, Bulearca AM, Scorei RI. Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life. Nutrition. 2013 Jan;29(1):178-83. Epub 2012 Nov 13.

(7.) Rogoveanu OC, Mogojanu GD, Bejenaru C, Bejenaru LE, Croitoru 0, Neamtu J, Pietrzkowski Z, Reyes-Izquierdo T, Bifa A, Scorei ID, Scorei Rl. Effects of calcium fructoborate on levels of C-reactive protein, total cholesterol, low-density lipoprotein, triglycerides, IL-1[beta], IL-6, and MCP-1: a double-blind, placebo-controlled clinical study. Biol Trace Elem Res. 2015 Feb;163(1-2):124-31. Epub 2014 Nov 30.

(8.) Pietrzkowski Z, Phelan MJ, Keller R, Shu C, Argumedo R, Reyeslzquierdo T. Short-term efficacy of calcium fructoborate on subjects with knee discomfort: a comparative, double-blind, placebo-controlled clinical study. Clin Interv Aging. 2014 Jun 5;9:895-9. eCollection 2014.

(9.) 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 Dec;144(1-3):253-63. Epub 2011 May 24.

(10.) Scorei ID, Scorei RI. Calcium fructoborate helps control inflammation associated with diminished bone health. Biol Trace Elem Res. 2013 Dec;155(3):315-21. Epub 2013 Aug 28.

(11.) Scorei IR. Calcium fructoborate: plant-based dietary boron as potential medicine for cancer therapy. Front Biosci (Schol Ed). 2011 Jan 1;3:205-15.
Table 1. Effects of calcium fructoborate and resveratrol on
cardiovascular markers and angina. (6)

Groups            Decrease   N-terminal     Lipids         Angina
(n = 29 per          in      prohormone                   Attacks
group)              CRP      at 60 days

1. Resveratrol                 <59.7%

2. Resveratrol     <30.3%      <65.5%                   <49.8% in 60
   plus calcium                                             days

3. Calcium         <39.7%      <52.6%     <5.9% TChol
   fructoborate                            <9.2% LDL
                                           >5.1% HDL

4. Controls

Table 2. Effects of calcium fructoborate at two different dosages on
markers of cardiovascular health. (7)

Group         CRP     Homocysteine      TChol       TG      LDL


CF-1         <31.3%      <5.5%       Significant   <9.1%   <9.8%
112 mg day                            reduction

56 mg day                                          <8.8%   <9.4%

Group           HDL      IL-lb       IL-6       MCP-1


CF-1         Increased   <29.2%   Significant   <31%
112 mg day                         reduction

56 mg day                                        26%
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Author:Stine, Jerry; Faass, Nancy
Publication:Townsend Letter
Date:May 1, 2016
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