Welcome to the March 2019 edition of Thorne’s Research Extracts. This is Thorne’s monthly research update on diet, nutrient, botanical, and lifestyle approaches to good health. Knowing that busy practitioners can’t always focus on the latest research, our medical team of NDs, MDs, PhDs, RDs, and MS (Biol) has summarized the essence of the most interesting studies.

In this issue: (1) fasting and the metabolome, (2) cultural differences in health-promoting activities, (3) fluoride exposure and male sex hormones, and (4) xenobiotics in dental floss.


Evidence for broad metabolic effects from fasting

In a small pilot study with four individuals, untargeted metabolomics was used to identify novel biomarkers attributable to fasting in blood, plasma, and red blood cells over a 58-hour period.

In addition to identifying 14 known biomarkers, researchers identified 32 additional metabolites that were significantly altered in the participants over the study period.

All but two, aspartate and gluconate, increased with fasting, although some reached their peak as soon as the 34-hour time point.

Among the identified biomarkers, organic acids, acylcarnitines, and branched-chain amino acids are associated with increased mitochondrial activation. 

Butyrates are associated with fuel substitution (and provide the primary fuel for the colonocytes of the large intestine), while sugar metabolites signal gluconeogenesis. Increased purines, pyrimidines, and amino acids support enhanced RNA and protein synthesis needed for metabolic reprogramming.

The pentose phosphate pathway helps maintain redox balance, while coenzymes support metabolic pathways.

The most novel finding in the study is the up-regulation of antioxidants (ergothioneine, ophthalmic acid, carnosine), presumably for offsetting increased oxidative stress due to the other metabolic adjustments that occur during fasting.

Contributed by Sheena Smith, MS (Biol)

  • Teruya T, Chaleckis R, Takada J, et al. Diverse metabolic reactions activated during 58-hr fasting are revealed by non-targeted metabolomic analysis of human blood. Sci Rep 2019;9(1):854. doi:10.1038/s41598-018-36674-9

Cultural differences inform how activities affect health

A recent paper published in Emotion takes a deep dive into two distinct pathways that lead to positive feelings. The paper analyzed survey data from 640 American and 382 Japanese subjects and revealed some interesting findings about what makes individuals from different cultures “feel good.”

In short, Americans tend to benefit from high stimulus activities, such as an active party or a fitness class; whereas, Japanese subjects are more likely to feel good when participating in lower stimulus activities, like taking a bath or reading.

Although these are contrasting pathways to feeling good, the study found both pathways work within their respective populations. Participating in high arousal positive (HAP) activities – which are preferred by Americans – predicted a lower BMI and lower inflammation scores in the U.S. cohort but not the Japanese cohort.

Frequent engagement in HAP activities was predictive of fewer symptoms of ill health, fewer sleep problems, and fewer reports of pain – but in American subjects only.

>On the other hand, frequent engagement in low arousal positive (LAP) activities was linked to better overall health, improved sleep, and less pain in the Japanese population.

However, frequent engagement in LAP activities was a strong predictor of psychological wellbeing in both groups. Surprisingly, frequent LAP activity was a stronger predictor of positive mental wellbeing in the American cohort than in the Japanese cohort.

The authors conclude that understanding the context of what it means to “feel good” and the frequency at which subjects engage in feel-good activities is essential to quantifying the positive impact activities have on physical and mental health.

Contributed by Joel Totoro, RD 

  • Clobert M, Sims T, Yoo J, et al. Feeling excited or taking a bath: Do distinct pathways underlie the positive affect-health link in the U.S. and Japan? Emotion 2019 Jan 24. doi:10.1037/emo0000531

Environmental fluoride exposure and genetic polymorphism effects on male sex hormones

Chronic exposure to fluoride can cause neurotoxicity and perhaps reproductive toxicity. Excessive fluoride exposure affects the hormones involved in the hypothalamic-pituitary-testicular (HPT) axis.

Epidemiological research suggests that testosterone is affected by sex hormone-binding globulin (SHBG) and androgen binding protein (ABP), and that both the HPT axis and the effect of fluoride exposure can be affected by certain ESRα gene polymorphisms.

A new Chinese study assessed the influence of exposure on gene polymorphisms that affect alterations in SHBG and ABP.

In this cross-sectional study, male farmers (ages 18-55) were grouped by low (n=116) and high (n=232) fluoride exposure from their drinking water over the previous 5-year period; groups were similar in demographics and considered healthy.

The high fluoride exposure group had significantly higher prevalence of dental fluorosis, urinary fluoride levels, and lower levels of SHBG.

No differences were found between groups in ABP, but SHBG did affect ABP levels. In addition, those with different SNPs at the XbaI and rs3798577 loci of the ESRα gene within the same exposure group had different serum ABP levels.

These findings suggest that chronic fluoride exposure from drinking water might be associated with alterations of serum SHBG and ABP concentrations.

The impact fluoride has on ABP levels varies depending on individual genetic variations, but can have a significant impact on human health. Low levels of SHBG in men have been associated with acne, hypertension, fluid retention, heart disease, and other adverse health conditions.

Contributed by Laura Kunces, PhD

  • An N, Zhu J, Ren L, et al. Trends of SHBG and ABP levels in male farmers: Influences of environmental fluoride exposure and ESR alpha gene polymorphisms. Ecotoxicol Environ Saf 2019;172:40-44.

Is flossing your teeth making you sick?

A class of fluorine compounds – per- and poly-fluoroalkyl substances (PFASs) – are used in a number of household products because they resist water and fats (grease), which makes them good candidates for non-stick cookware, stain-resistant carpet and furniture upholstery, food packaging, and outdoor performance wear.

Two of these compounds in particular – perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) – have been linked to serious health conditions, including thyroid disease and decreased sex hormones and growth hormone in children, and kidney and testicular cancer, decreased semen quality, and ulcerative colitis in adults.

In a recent study, 178 U.S. women, ages 40-60, were questioned regarding nine behaviors associated with possible exposure to PFASs, including consumption of fish and shellfish, use of non-stick cookware, use of certain types of dental floss, consumption of microwave popcorn, exposure to stain-resistant carpet or furniture, and eating food from coated cardboard containers.

The participants were tested for blood levels of six different PFASs. The city water supplies of the participants were also tested for PFASs.

The study found significant associations between PFASs blood levels and use of dental flosses that use a PFAS coating to improve glide, consumption of food from PFAS-coated cardboard containers, exposure to stain-resistant carpet or furniture, and drinking water contaminated with PFASs.

The other factors – non-stick cookware, eating microwave popcorn, and fish/shellfish consumption – did not have a significant relationship in this study. Of 18 dental flosses tested, six tested positive for fluorine compounds, including Oral B Glide, two others marketed as “glide” floss, two marketed as “compare to Oral B Glide,” and one advertised as containing single Teflon® strands.

Contributed by Kathi Head, ND

  • Boronow K, Brody J, Schaider L, et al. Serum concentrations of PFASs and exposure-related behaviors in African American and non-Hispanic white women. J Expo Sci Environ Epidemiol 2019;29(2):206-217.