Welcome to the October 2019 issue of Thorne’s Research Extracts – designed to keep busy practitioners and savvy consumers up-to-date on the latest research on diet, nutrients, botanicals, the microbiome, the environment, and lifestyle approaches to good health. Our medical team, which includes NDs, MDs, PhDs, RDs, and an MS, LAc, and CCN, has summarized the essence of several of the most interesting studies.

Research summaries in this issue include: (1) timing of supplements for best workout results, (2) best protein combinations for muscle growth, (3) contamination of one-third of CBD products on the market, and (4) acetaminophen during pregnancy and behavioral issues in offspring.

Timing of ergogenic aids and micronutrients on muscle and exercise performance

Contributed by Laura Kunces, PhD, RD

A recent paper reviewed the latest research on muscle adaptations and performance benefits based on specific timing of selected ergogenic aids and micronutrients. The findings provide significant direction for an individual training regimen throughout a season.

In summary:

  • Caffeine at 100-300 mg (or 3-6 mg/kg body weight) should be consumed within two hours of exercising because of caffeine’s fast action and rapid clearance from the bloodstream. Caffeine has shown benefits for improving fat utilization, mental strength, muscular strength, and endurance, and decreasing fatigue – improving overall performance.  
  • Nitrates (such as in beetroot juice) dosed per manufacturer recommendations (because not all juices are of equal potency) should be consumed within 2-3 hours of exercising for best effects at improving endurance and intermittent exercise capacity. Nitrates, which work in the body’s nitric oxide pathway, increase blood flow and muscular contractility while decreasing the oxygen required during endurance exercise.
  • Creatine at a maximum dose of five grams (or 0.1 g/kg body weight) for 10-12 weeks improves high-intensity exercise capacity, muscle mass, and strength by increasing phosphocreatine and ATP production.*
  • Iron at 100 mg/day for 3-6 weeks favorably impacts oxygen-carrying capacity and endurance exercise performance.*
  • Beta-alanine at 1.3-1.6 grams consumed four times during the day for a daily total of 6-7 grams on days of high-intensity exercise and resistance training decreases neuromuscular fatigue.*
  • Calcium at 1,000 mg/day should be consumed within one hour of exercising for up to 12 months to support bone density and balance parathyroid hormone levels.* 
  • Sodium bicarbonate at 0.3 g/kg body weight consumed within 1-3 hours of exercising can mitigate the metabolic acidosis that occurs during high-intensity exercising. 

  • Stecker R, Harty P, Jagim A, et al. Timing of ergogenic aids and micronutrients on muscle and exercise performance. J Int Soc Sports Nutr 2019;16(1):37. doi: 10.1186/s12970-019-0304-9

Low-dose protein with added leucine stimulates myofibrillar protein synthesis compared to a high-dose protein intake.

Contributed by Joel Totoro, RD

In a double-blind study, researchers at McMaster University and the Nestle Research Centre clarified how protein consumption optimizes myofibrillar protein synthesis (MPS) in young men. Although existing studies show the impact of whole protein, branch-chain amino acids (BCAA), and leucine, this study compared consumption of protein of varying formulations to examine which formulation best supports maximum MPS. 

Forty men (ages 18-35; average age 21) on a standardized diet and exercise program were randomly assigned to one of five groups based on protein content:

  • Low protein (6.25 grams whey protein)
  • Low protein + low leucine (6.25 grams whey protein + 3.0 grams leucine)
  • Low protein + BCAA (6.25 grams whey protein + BCAA blend with 5.0 grams leucine)
  • Low protein + high leucine (6.25 grams whey protein + 5 grams of leucine)
  • High protein (25 grams whey protein)

Each protein combination positively impacted MPS (measured by muscle biopsy) in the immediate postprandial period (0-1.5 hours); however, only the low-protein + high-leucine and the high-protein groups reached optimal MPS in the 1.5-4.5 hour postprandial period. The study showed no significant difference in MPS between either low-protein + leucine group and the high-protein group, the latter of which consumed four times the amount of protein.

This study is unique in that the protein feeds were mixed with a standardized nutrient beverage containing carbohydrates and fat, which is common in a real-world setting. Although previous work has shown that, when consumed in isolation, three grams of leucine stimulated MPS, this study suggests that when consumed in a mixed nutrient feed, five grams of leucine optimally promotes maximum MPS.  

  • Churchward-Venne T, Breen L, Di Donato D, et al. Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial. Am J Clin Nutr 2014;99(2):276-286.

One-third of CBD products tested positive for synthetic cannabinoids; others had no CBD

Contributed by Jacqueline, Jacques, ND

Cannabidiol (CBD) has become extremely popular in the past few years, leading to a proliferation of CBD products – from capsules to creams to vape cartridges.  But the commercial CBD boom in has brought with it numerous concerns about product safety and quality. For example, a 2017 study in the Journal of the American Medical Association suggests that one-third of products sold as hemp or CBD are mislabeled.

In addition, dangerous synthetic cannabinoids being labeled as safe, natural products are now common and pose a more serious risk, and has been discussed previously in this magazine. For example, both Utah and Tennessee have reported cases of individuals being poisoned by the synthetic cannabinoid, 4-cyano CUMYL-BUTINACA (4-CCB). More recently, the Associated Press sampled CBD products from 13 companies, including edibles and vaping products, commissioning Flora Research Labs in Oregon to test them for CBD and THC content, as well as the presence of synthetic cannabinoids.

Of 350 products tested, 128 tested positive for the presence of adulterants. Most of the adulteration was synthetic cannabinoids, although three samples tested positive for the powerful opiate Fentanyl. In addition, many products tested well below the label claim for CBD content, including some that had no CBD. These results should underscore for anyone purchasing hemp or CBD products that adulteration is both widespread and common – so purchasing from reputable brands is critical

You can read more about the study and how data was collected here:


Hyperactivity and behavioral difficulties were associated with acetaminophen use during pregnancy.

Contributed by Alan Miller, ND

Acetaminophen use for pain and fever relief goes back to 1955, when McNeil Laboratories introduced it in the United States. It became an over-the-counter (OTC) drug in 1960 and is now sold by itself or combined with numerous other drugs, both prescription and OTC. Acetaminophen dosing has long been linked to liver toxicity; in fact, it is now the number one cause of liver failure in the United States. Because of this, in 2009, the U.S. Food and Drug Administration began requiring a warning on acetaminophen-containing OTC medications, describing the potential for liver toxicity and advising consumers to not take it if they drink alcohol. 

Other known concerns regarding acetaminophen use include asthma, skin rashes and other skin reactions, and childhood behavioral and cognitive issues. In addition, epidemiological studies on its use during pregnancy show a possible increased risk of autism.

A new study in a special issue of Pediatric and Perinatal Epidemiology, focusing on acetaminophen and neurodevelopment, looked at the risk of childhood behavioral and cognitive issues in children whose mothers took acetaminophen between weeks 18 and 32 of their pregnancies.

These researchers found, in a cohort of the Avon Longitudinal Study of Parents and Children, that maternal use of acetaminophen significantly increased the risk of 12 cognitive and behavioral outcomes, which included, “being less adaptable at six months, having poorer persistence at 24 months, having elevated scores on the hyperactivity behavior scales at 42 and 47 months (maternal reports), and teacher reports of poor attention in school year 3 (7-8 years).”

Hyperactivity and behavioral difficulties were also associated with acetaminophen use during pregnancy. These outcomes, however, did not persist past age 11.

The researchers did not expound on the potential cause of these associations, although they did eliminate confounding circumstances.  With other safe options for pain and fever reduction during pregnancy, it is astounding that this drug, which is well known to have significant safety issues in many areas, would ever be used in pregnancy.

  • Golding J, Gregory S, Clark R, et al. Associations between paracetamol (acetaminophen) intake between 18 and 32 weeks gestation and neurocognitive outcomes in the child: A longitudinal cohort study. Paediatr Perinat Epidemiol September 2019:00:1-10. https://doi.org/10.1111/ppe.12582