fat burning, type 2 diabetes, Uncategorized

NDGA and diet induced obesity

Larrea tridentata, the creosote bush of the US Southwest, goes by many names:  chaparral, greasewood,  gobernadora, and  hediondilla. I’ve been told that these bushes are responsible for the sweet smell that fills the air after monsoon storms.

A good overview

in 2010 Lü and coworkers at Baylor College of Medicine Houston published a short review on nordihydroguaiaretic acid (NDGA), a metabolite of the creosote bush.  Five to ten percent of the dry weight of the creosote leaves may be NDGA.  NDGA constitutes 80% of the phenolics that include flavanoids and other lignans.   This review covers reactive oxygen and nitrogen species scavenging abilities. The ability to  cross-link collagen was mentioned as a tissue engineering application.  Potential medicinal uses were summarized.  Toxicity studies had been conducted, but there was still a lot not known in 2010.

One theme of this review is the ability of NDGA to inhibit cyclooxygenase and lipoxygenase pathways, specifically  5-lipoxygenase.

A recent study

A study out of the Geriatrics Research, Education and Clinical Center, Veterans Affairs Palo Alto Health Care System in Palo Alto, California gives us North Americans reason to look a  bit closer.  Chan and coworkers fed male mice standard chow or a American lifestyle-induced obesity syndrome (ALIOS) diet.

At six weeks of age, mice were divided into three groups

  • standard chow
  • ALIOS
  • ALIOS + 2.5 g NDGA per kg feed

The ALIOS diet is a modified high-fat diet with 45% of the caloric content derived from fats.   Two thirds of this fat is from  partially hydrogenated vegetable oil

  • 28% saturated
  • 57% monounsaturated
  • 13% polyunsaturated fatty acids

To add insult to injury,  Chan and coworkers spiked the drinking water of the mice on the ALIOS diet with high-fructose corn syrup equivalents (55% fructose, 45% glucose) at 42 g/l.

Needless to say, these mice got fat and developed metabolic issues.

creosote1
An exert from Chan (2018) showing that mice on NDGA gained less weight on the ALIOS American diet in spite of similar caloric intake.  ***P < 0.001 vs. chow; ****P < 0.0001 vs. chow; †††P < 0.001 vs. ALIOS. ANOVA, analysis of variance

An ongoing debate is whether the BMI is a good index of  visceral fat.  Epidymal fat is used as a surrogate for visceral fat because they increase together.  Those that have dissected rodents with visceral obesity know that this fat is all over the small and large intestines as well as the caecum/appendix.  An up and coming in vitro diagnostic company, Randox, is working on tests to detect visceral obesity.  Their cartoon of human visceral obesity speaks volume of the danger just in the mechanics of removing an inflamed appendix..

Imges of epidymal and visceral fat. NDGA from creosote decreeases epidymal fat on mice on American diet
Left Rodent epidymal fat is easy to dissect and is used as a surrogate for visceral fat. Center Human visceral fat covers the intestines. Right NDGA from creosote decreases epidymal fat in mice on the ALIOS American diet.  ***P < 0.001 vs. chow; ****P < 0.0001 vs. chow; †††P < 0.001 vs. ALIOS

Other highlights of this paper

  • Glucose and insulin tolerance were improved in ALIOS + NDGA mice compared to ALIOS alone mice, but they did not return to the chow baseline.
  • Two common liver enzymes (ALT and AST)  found in the blood after injury were statistically the same as the chow control.
  • NDGA induced  increases in  enzymes involved in fatty acid oxidation and decreases in enzymes in lipid synthesis.
  • Some anti-oxidant enzymes were also increased.

The scientific literature is full of studies like that of Chan and coworkers (2018) that cannot be explored in a single blog.  The applications in the Lü (2010) review have been expanded upon in more recent literature.  NGDA is without question a small molecule with a lot of promise.  Because it is bioactive, the consumer should consider using it under the supervision of a medical professional.

Another caution

NDGA is on the US FDA’s food additive list:

  • Nordihydroguaiaretic acid (NDGA) – AOX, ILL, Not legal for use in foods – 189.165

With all of the biological activities attributed to NDGA in the literature, the consumer probably doesn’t want this small molecule in a long list of ingredients in processed foods that usually get ignored.

Where to buy

You can buy NDGA at Arizona Natural.

References

Chan JKW, Bittner S, Bittner A, Atwal S, Shen WJ, Inayathullah M, Rajada J, Nicolls MR, Kraemer FB, Azhar S. (2018) Nordihydroguaiaretic Acid, a Lignan from Larrea tridentata (Creosote Bush), Protects Against American Lifestyle-Induced Obesity Syndrome Diet-Induced Metabolic Dysfunction in Mice. J Pharmacol Exp Ther. 365(2):281-290  Free Paper

Lü JM, Nurko J, Weakley SM, Jiang J, Kougias P, Lin PH, Yao Q, Chen C.(2010) Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: an update.   Med Sci Monit. 16(5):RA93-100.  Free Paper

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