Aside from its H. pylori eradication powers …

Mastic Lowers Cholesterol and Glucose Levels
… and it does so in healthy volunteers with the right dose
By Will Block


Not snow, but mastic tears
Only a few ancient herbal cures have survived the journey from their initial identification through to modern day. One such substance is mastic gum, (hereafter mastic) a resin collected from Pistacia lentiscus, an evergreen shrub found on the Greek island of Chios in the Aegean Sea (this island is alleged to be the one-time residence of Homer). Mastic has been used as a medicine since antiquity. In ancient Greece, it was given as a remedy for snakebite, and, in India and Persia, it was used to fill dental cavities. In fact, it is still used in traditional folk medicine of the Middle East.

Historical Endorsements

Hippocrates, the “Father of Western Medicine,” claimed that mastic helps prevent digestive problems and colds, and he did so in the fifth century BCE. While little is known about Hippocrates, he is credited with an oath to uphold specific ethical standards, one that has been historically (and is still) taken by physicians. “First do no harm,” is but one tenet. During the first century, Greek physician Dioscorides wrote about the healing properties of mastic in his 5-volume encyclopedia De Materia Medica (“On Medical Material”). This momentous work about herbal medicine (a pharmacopeia) was widely read for more than 1,500 years.

Prescient Recognition of Mastic

In the second century, Galen (“the best physician is also a philosopher”) presciently endorsed mastic for disorders of the stomach and intestine. During the Renaissance, especially during plague years, mastic was highly recommended. And it might have worked to some degree (see “Mastic: Curtains for Ulcer-Causing Bacteria” in the January 2010 issue of Life Enhancement Magazine). Francis Bacon, a contemporary of Shakespeare, who established and popularized an inductive methodology for scientific inquiry, endorsed mastic’s use.

References


If spices were worth their
weight in silver, by Columbus’
estimate, mastic was worth its
weight in gold. Nonetheless, the
“discovery” proved to be an error.


Mastic’s Role in the Discovery of the New World

During 1493, Christopher Columbus wrote a letter to the Treasurer of Aragon (which was thus intended for the eyes of his sponsors, Ferdinand and Isabella) announcing his discovery of mastic in the New World. If spices were worth their weight in silver, by Columbus’ estimate, mastic was worth its weight in gold. Nonetheless, the “discovery” proved to be an error.

The Power of Mastic

To help explain much of what it can do, mastic contains antioxidants and also has antibacterial and antifungal properties. It also has hepatoprotective (liver-protective) benefits. The core study attracting interest in its ability to fight Helicobacter pylori, an ulcer-causing bacteria, was published in the New England Journal of Medicine at the end of 1998.1 Other studies have indicated that mastic has an ability to eliminate H. pylori,2 but have also suggested that refining mastic by removing the polymer poly-β-myrcene may make the active components, particularly isomasticadienolic acid, more available and effective.3 This has been proven to be wrong (see below). Mastic may also have some value in preventing tooth decay4 and gingivitis,5 as chewing mastic reduces oral bacteria.


Administration of polymer-free mastic
and high mastic (2 g/day)
resulted in no alteration.


Cholesterol Lowering and Other Benefits

Another study found that high consumption of mastic results in decreased levels of total serum cholesterol, LDL, total cholesterol/HDL ratio, lipoprotein (a), apolipoprotein A-1, and apolipoprotein B.6 It also lowered ALT, AST, and GGT (signs of a distressed liver). Mastic oil is widely used in the preparation of ointments for skin disorders and afflictions. In the past, it was also used in the manufacture of adhesive bandages.

Healthy Volunteers Find Benefits

A new study (CHIOS-MASTIHA) notes that mastic gum possesses anti-oxidant, anti-inflammatory, and anti-atheromatic (able to break down an accumulation of degenerative material in the inner layer of artery walls), along with lipid- and glucose-lowering properties.6

This study evaluated the effects of different doses of mastic on cholesterol and fasting plasma glucose levels of healthy volunteers, with a mean age of 53 years. In it—a prospective, placebo-controlled scientific inquiry—156 volunteers (93 of which were women) with total cholesterol levels >200 mg/dl were randomized into four groups:

  1. a placebo control group (n=23)

  2. a low mastic group receiving daily 1 g of mastic (330 mg capsules, three time daily) (n=72)

  3. a polymer-free mastic group, receiving daily a total dose of 1 g of polymer-free mastic (330 mg caps, three time daily (n=33)

  4. a high mastic group receiving daily a total dose of 2 g mastic, taken all at once (n=28)

Reduction of Cholesterol and Fasting Plasma Glucose Levels

After eight weeks, the low mastic group (1 g/day) reduced total cholesterol by 11.5 mg/dl and the fasting plasma glucose group by 4.5 mg/dl. Not bad.

The effect was stronger in overweight and obese patients (with a BMI>25), with an estimated mean reduction of total cholesterol by 13.5 mg/dl and fasting plasma glucose by 5.1 mg/dl. Administration of polymer-free mastic and high mastic (2 g/day) resulted in no alteration.

While no effect was observed on LDL, HDL, triglycerides, uric acid or C-reactive protein (CRP—a measure of inflammation), there were no adverse events recorded. Mastic has a significant lowering effect on total cholesterol and glucose levels of healthy volunteers, with excellent tolerance and no side effects, especially in overweight and obese individuals.


Mastic has a significant lowering
effect on total cholesterol and glucose
levels of healthy volunteers, with
excellent tolerance and no side
effects, especially in overweight and
obese individuals.


The Devastation of Cardiovascular Disease

Cardiovascular disease is the worldwide leading cause of morbidity and mortality. Less well known: atherosclerosis—the main pathological process leading to coronary, cerebral and peripheral artery disease—begins early in life and progresses by certain cardiovascular risk factors like tobacco use, unhealthy diet and physical inactivity (resulting in obesity), hypertension, dyslipidemia and type 2 diabetes.



Columbus voyaged to Chios before venturing into the Atlantic Ocean. Mastic was so highly valued in Old World medicine that on his first trip to the New World a reward of a gold doubloon was offered to the first crewmember who could find it in the Indies. A seaman on board the Niña claimed that reward by first sighting “mastic” on November 5, 1492 on the island of Cuba. This later proved to be false.

Noteworthy studies both in primary and in secondary prevention have proved that pharmaceutically reduced cholesterol levels decrease the incidence of adverse cardiovascular events. As far as diabetes is concerned, the cardiovascular risk increases early, prior to the development of overt diabetes, due to changes in vasculature. This poses a great need to intercept the vicious cycle of hyperglycemia—vascular disease at an earlier stage, i.e., the stage of “pre-diabetes,” before the development of clinical manifestations and organ damage.

While pharmaceuticals have played a large role in much of the primary and in secondary prevention literature mentioned above, they have many side effects. This is far less so with natural remedy herbals such as mastic which is increasingly thought to possess lipid and glucose lowering effects, although scientific evidence of proven efficacy is not as prevalent (of course, because Big Pharma pays for the so called “gold standard” tests). In the CHIOS-MASTIHA study, natural mastic from the southern part of Chios—the only place on the planet where mastic trees are systematically cultivated and mastic gum is produced and exploited commercially—was used.

Archaeological findings and historical references establish the medicinal, cosmetic and culinary use of mastic gum in the Mediterranean basin since the seventh century BC (just after the time of Homer). In the modern era, mastic has been increasingly the subject of scientific research, and many beneficial biological activities—anti-indigestion, anti-ulcer (acting against Helicobacter pylori), antimicrobial, antifungal, antioxidant, hypolipidemic, anti-inflammatory, anti-Crohn’s disease and anti-neoplasmatic (anti-cancer)—have been reported (search Life-Enhancement.com for “mastic,” where 150 articles may be found).

Mastic Composition

Mastic’s main components are an insoluble polymer (25%) and a triterpenic fraction (67%), which are further sub-classified as acidic (39%) and neutral (28%) fractions.7,8,9 The acidic fraction seems to have the greatest anti-microbial activity and its main components are the masticadienonic acid (30%), isomasticadienonic acid (30%), oleanonic acid (15%) and moronic acid (10%).

The neutral fraction’s main components include butyspermol, tirucallol, oleanolic aldehyde, oleanonic aldehyde, and betulonal. Neutral compounds like butyspermol and tirucallol present a typical phytosterolic structure.11 Another monoterpenic constituent of mastic, camphene, seems to possess promising hypo­lipidemic activity.12 Furthermore, the anti-oxidant effects of Chios mastic, which may result in reducing LDL cholesterol oxidation, could be attributed to the resin’s remarkable concentration of various polyphenols.13 Mastic is a natural anti-oxidant, extremely efficient in preventing LDL oxidation in vitro and its hypolipidemic effect has been demonstrated in animal and human studies. Mastic could be a potential antidiabetic agent, as is the case with many other natural products rich in terpenes. Mastic also exhibits remarkable anti-inflammatory activity.


Restoration of intracellular
glutathione (GSH) and down-
regulation of CD36 expression are
possible pathways for mastic
triterpenes to exert their antioxidant
and antiatherogenic effects.


Summary of Findings

Returning to the CHIOS-MASTIHA study, after 8 weeks low mastic (1 g taken in 3 equally divided caps throughout the day) administration resulted in a mean reduction of total cholesterol by 11.5 mg/dl, triglycerides by 29.4 mg/dl, and free plasma glucose by 4.5 mg/dl.

Further analysis revealed that the effect was stronger in overweight and obese subjects (BMI>25) receiving low mastic, with an estimated mean reduction of total cholesterol by 13.5 mg/dl and fasting plasma glucose by 5.1 mg/dl, adjusted for age, gender, BMI and baseline values.

Figure 1: Effects of the different mastic formulations on total, LDL and HDL cholesterol, triglycerides and glucose levels, compared to placebo, among hyperlipidemic individuals (n=156).
LEM1512Cholesterol-chart274.jpg
(click on thumbnail for full sized image)

Yet, polymer-free mastic caps administration resulted in no effect on LDL-cholesterol, HDL-cholesterol, triglycerides, uric acid or CRP values.

On the other hand, high mastic power administration (2 g/day, all at once) resulted in no significant effects for total cholesterol or free plasma glucose, but did serve to lower triglycerides (see Fig. 1).

No changes were documented for BMI during the study, in any of the groups. No gastrointestinal adverse events were reported. Furthermore, there was no liver or renal toxicity.

These results found that high mastic surpassed low mastic for triglycerides, but not for total cholesterol or free plasma glucose levels.

First Human Study Comparing the Action of Three Different Mastic Formulations

CHIOS-MASTIHA is the first human in vivo, prospective, randomized, placebo-controlled, pilot study comparing the action of three different formulations of mastic on lipid and glucose metabolism of otherwise healthy, hypercholesterolemic volunteers.


In the low-dose group (0.7 g of
mastic in solution) a decrease in
glucose levels among male subjects
was observed.


Biological Actions of Mastic [Technical]

There are several possible biological mechanisms to explain mastic effects on lipid and glucose metabolism. Restoration of intracellular glutathione (GSH) and down-regulation of CD36 expression are possible pathways for mastic triterpenes to exert their antioxidant and antiatherogenic effects. Camphene, one of mastic’s triterpenic compounds, in synergy with other mastic constituents demonstrates a significant hypolipidemic effect, possibly via lipoprotein lipase (LPL) activation.

Mastic seems to act as a PPAR-γ (and possibly a PPAR-α) agonist affecting lipid and glucose metabolism. Some mastic triterpenic constituents could act as α-glucosidase inhibitors, while others demonstrate phytosterolic effects. Triterpenes are also known to exert beneficial effects on pancreatic b-cells, enhancing insulin secretion, and to inhibit protein tyrosine phosphatase-1B (PTP-1B) enhancing insulin action.

One in vitro mastic study compared several naturally-occurring gums and resins, and concluded that mastic was the most effective in protecting human LDL from copper-induced oxidation in vitro.

Another study proved that the neutral fraction of mastic inhibits in vitro the expression of endothelial adhesion molecules (VCAM-1, ICAM-1) and other inflammatory mediators in human aortic endothelial cells, thus interfering with the initial stages of atherosclerosis.


In the current study low mastic
capsules at a daily dose of 1 g
produced the most beneficial effects
regarding total cholesterol and free
plasma glucose.


Animal Studies

Administration of mastic in hypercholesterolemic rabbits resulted in reduced total cholesterol levels and prevented subintimal (the innermost membrane or lining of some organ or part) accumulation of lipids and foamy macrophages. Peripheral anti-inflammatory and anti-oxidant activities of mastic have also been reported in the limbs of mice and rats, although the mechanism of action was not fully elucidated.

Another study demonstrated that camphene, a monoterpenic compound of mastic, reduced total and LDL cholesterol and triglycerides in hyperlipidemic rats.12 The authors of this study suggested that the hypolipidemic action of camphene was independent of HMG-CoA reductase activity, which is the main mechanism of action of statins.

In a recent study, mastic significantly lowered total cholesterol, LDL, triglycerides and glucose levels, and improved HDL cholesterol levels and hepatic steatosis (the abnormal retention of lipids within a cell) in diabetic mice.14

Human Studies

The only in vivo human study of mastic (not placebo controlled) included 133 volunteers of both genders, randomized to two groups, one receiving daily 5 g of mastic powder for a period of 18 months and a second group, receiving daily 0.7 g of mastic in an aqueous solution for 12 months.6

In the high dose group (5 g mastic powder per day) total cholesterol, LDL, total cholesterol/HDL ratio, apoA, apoB, Lp(a), AST, ALT and gamma-GT levels were significantly decreased, while glucose, HDL and triglyceride levels did not exhibit significant changes. Total cholesterol, total cholesterol/HDL ratio and AST were reduced in males, while only Lp(a) was reduced in females. In the low-dose group (0.7 g of mastic in solution) a decrease in glucose levels among male subjects was observed.


The fact that mastic powder was
administered once daily could be the
cause of its failure.


Effect of Mastic Formulations in Current Study

To repeat, in the current study the administration of mastic capsules at 1 g/day resulted in a reduction of total cholesterol levels by 11.5 mg/dl. This effect was stronger in overweight and obese patients (mean BMI=28.5 kg/m2) with an estimated mean reduction of total cholesterol by 13.5 mg/dl.

A trend for reduction was observed for LDL-cholesterol (-6.0 mg/dl), HDL-cholesterol (-3.2mg/dl), triglycerides (-4.7 mg/dl) justifying the reduction in total cholesterol levels.

The absence of any effect on LDL-cholesterol and on triglycerides levels is in contrast to all the aforementioned literature, where LDL reduction was a stable finding in animals. The only in vivo human study of mastic (not placebo controlled)13 also showed some degree of LDL reduction, but with a much higher mastic powder dose (5 g compared to 2 g in the current study). Triglyceride levels were also not affected by any mastic formulation, in contrast with some animal studies, but in accordance with the other human study. Favorable effects on glucose levels from the use of mastic have been shown so far in diabetic mice and the only other human study in male volunteers.13

In the present study, low mastic reduced free plasma glucose levels in healthy volunteers by 4.5 mg/dl. This effect was stronger in overweight and obese patients, with an estimated mean reduction of free plasma glucose levels by 5.1 mg/dl. Total mastic powder and polymer-free mastic caps did not show any favorable effect, in agreement with the results by the other human study where 5 g of mastic powder did not exhibit any changes in glucose levels of 133 volunteers (including subjects with diabetes) for an 18-month follow-up period.

However, in the aforementioned study,6 a mastic solution of about 0.7 g of mastic decreased glucose levels, but only in males, by 3.1 mg/dl. In the current study low mastic capsules at a daily dose of 1 g produced the most beneficial effects regarding total cholesterol and free plasma glucose. Failure to reduce serum levels of LDL cholesterol and triglycerides could be attributed to the relatively low dose.


The CHIOS-MASTIHA study
showed that mastic capsules with
the polymer in total daily divided
dose of 1 g have the most powerful
effect in lowering total cholesterol
and glucose levels in
healthy volunteers.


Higher Frequency Per Day May Make a Difference

A daily dose of 2 or 3 g could be more effective, as is the case in some of the aforementioned studies. Instead, mastic powder failed to produce any result, even though it was administered at a higher dose of 2 g daily. The fact that mastic powder was administered once daily could be the cause of its failure. Polymer free mastic capsules, despite the researchers’ hopes, failed also to produce any effect. This failure could be attributed to insufficient dose, different absorption rate in the GI tract, or to some unknown biological activity of the missing polymer.

In conclusion, the CHIOS-MASTIHA study showed that mastic capsules with the polymer in total daily divided dose of 1 g have the most powerful effect in lowering total cholesterol and glucose levels in healthy volunteers. The innovative finding of this study is the glucose-lowering effect of mastic in healthy volunteers. Per chance, 1 g of mastic is the generally recommended amount for H. pylori eradication. By taking mastic at 1 g/day in divided doses, you could “kill two birds” with one stone.

References

  1. Huwez FU, Thirlwell D, Cockayne A, Ala'Aldeen DA. Mastic gum kills Helicobacter pylori. N Engl J Med. 1998 Dec 24;339(26):1946.
  2. Dabos KJ, Sfika E, Vlatta LJ, Giannikopoulos G. The effect of mastic gum on Helicobacter pylori: a randomized pilot study. Phytomedicine. 2010 Mar;17(3-4):296-9.
  3. Paraschos S, Magiatis P, Mitakou S, Petraki K, Kalliaropoulos A, Maragkoudakis P, Mentis A, Sgouras D, Skaltsounis AL. In vitro and in vivo activities of Chios mastic gum extracts and constituents against Helicobacter pylori. Antimicrob Agents Chemother. 2007 Feb;51(2):551-9.
  4. Aksoy A, Duran N, Koksal F. In vitro and in vivo antimicrobial effects of mastic chewing gum against Streptococcus mutans and mutans streptococci. Arch Oral Biol. 2006 Jun;51(6):476-81.
  5. Takahashi K, Fukazawa M, Motohira H, Ochiai K, Nishikawa H, Miyata T. A pilot study on antiplaque effects of mastic chewing gum in the oral cavity. J Periodontol. 2003 Apr;74(4):501-5.
  6. Triantafyllou A, Chaviaras N, Sergentanis TN, et al. Chios mastic gum modulates serum biochemical parameters in a human population. J Ethnopharmacol. 2007;111(1): 43–9.
  7. Kartalis A, Didagelos M, Georgiadis I, Benetos G, Smyrnioudis N, Marmaras H, Voutas P, Zotika C, Garoufalis S, Andrikopoulos G. Effects of Chios mastic gum on cholesterol and glucose levels of healthy volunteers: A prospective, randomized, placebo-controlled, pilot study (CHIOS-MASTIHA). Eur J Prev Cardiol. 2015 Aug 26. pii: 2047487315603186. [Epub ahead of print] PubMed PMID: 26311707.
  8. Assimopoulou AN, Zlatanos SN and Papageorgiou VP. Antioxidant activity of natural resins and bioactive triterpenes in oil substrates. Food Chem. 2005; 92(4): 721–7.
  9. Braca A, Dal Piaz F, Marzocco S, et al. Triterpene derivatives as inhibitors of protein involved in the inflammatory process: molecules interfering with phospholipase A2, cycloxygenase, and lipoxygenase. Curr Drug Targets. 2011; 12(3): 302–21.
  10. Paraschos S, Magiatis P, Mitakou S, et al. In vitro and in vivo activities of Chios mastic gum extracts and constituents against Helicobacter pylori. Antimicrob Agents Chemother. 2007; 51: 551–9.
  11. Loizou S, Paraschos S, Mitakou S, et al. Chios mastic gum extract and isolated phytosterol tirucallol exhibit anti-inflammatory activity in human aortic endothelial cells. Exp Biol Med (Maywood). 2009; 34(5): 553–561.
  12. Vallianou I, Peroulis N, Pantazis P, et al. Camphene, a plant-derived monoterpene, reduces plasma cholesterol and triglycerides in hyperlipidemic rats independently of HMG-CoA reductase activity. PLoS One. 2011; 6(11):e20516.
  13. Mahmoudi M, Ebrahimzadeh MA, Nabavi SF, et al. Antiinflammatory and antioxidant activities of gum mastic. Eur Rev Med Pharmacol Sci. 2010; 14(9): 765–9.
  14. Georgiadis I, Karatzas T, Korou LM, Agrogiannis G, Vlachos IS, Pantopoulou A, Tzanetakou IP, Katsilambros N, Perrea DN. Evaluation of Chios mastic gum on lipid and glucose metabolism in diabetic mice. J Med Food. 2014 Mar;17(3):393–9.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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