Welcome to the March 2021 edition of Research Extracts. “The Extracts” is 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, an MS, an LAc, and an LPN, has summarized the essence of several of the most interesting recent studies.

In this issue you will find new studies on: (1) processed food consumption and heart disease risk, (2) caffeinated coffee and heart failure risk, (3) vitamin C and bleeding gums, and (4) sun exposure and hormone levels.

Ultra-processed food consumption increases cardiovascular disease risk

Cardiovascular disease (CVD) is the most common cause of death worldwide. Although the link between diet and CVD is well known, the connection between ultra-processed foods and CVD has not been well delineated. Ultra-processed foods are made from substances derived from additives in food. And although they contain little to no whole foods, ultra-processed foods dominate the food system.

A recent study of 155,000 U.S. adults, ages 55-74, investigated whether ultra-processed foods have a clearly delineated role in CVD and mortality. Participants were asked to complete a questionnaire regarding health and social status, dietary composition, and physical activity. Follow-up occurred approximately 14 years after the initial intake, during which time there were 5,490 cardiovascular related deaths.

The participants with the highest intake of ultra-processed foods were at increased risk of CVD and heart disease-related death. In addition, individuals with the highest intake of ultra-processed foods also had a higher rate of all-cause mortality. Interestingly, while the highest rates of intake were among men, the harmful association between ultra-processed foods and CVD was more pronounced in women. The authors suggest several explanations, including the protective effect of higher testosterone levels in men and the disparities in cardiovascular disease prevention, diagnosis, and treatment between men and women.

Contributed by Jennifer L. Greer, ND, MEd


  • Zhong G, Gu H, Peng Y, et al. Association of ultra-processed food consumption with cardiovascular mortality in the US population: long-term results from a large prospective multicenter study. Int J Behav Nutr Phys Act 2021;18(1):21. doi:10.1186/s12966-021-01081-3
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  • For more information on the disparities between women and men in heart disease, check out this new blog from Mayo Clinic.

Caffeinated coffee can decrease the risk for heart failure

Although much is known about modifiable risk factors for coronary heart disease and stroke, less is known about the risk factors for heart failure (particularly heart failure with a non-ischemic etiology). A recent retrospective analysis reviewed the risk factors either negatively or positively associated with coronary heart disease, heart failure, and stroke in three major studies – The Framingham Heart Study (FHS), the Cardiovascular Heart Study (CHS), and the Atherosclerosis Risk in Communities (ARIC) study. Although the three studies evaluated several dietary factors – butter versus margarine, red meat, eggs, whole milk, tea, cheese, wine, beer, cocktails, sugar, coffee, and decaffeinated coffee – coffee was the only dietary factor significantly associated with any of the outcomes across the three studies.

Increased caffeinated coffee consumption was associated with significantly decreased risk for heart failure all three studies. Regarding amount of daily coffee consumption, whereas, one cup daily compared to no coffee did not appear to confer protection, two or more cups daily did significantly decrease the risk for heart failure. Interestingly, decaffeinated coffee significantly increased the risk for heart failure.

The authors, however, caution the following: “The potential of intentional higher coffee consumption as a means of reducing HF [heart failure] risk cannot be determined from this analysis. It remains possible that coffee consumption is a marker or proxy for another behavior or dietary factor that reduces HF risk. Consequently, intentional or prescribed increase in coffee intake for the purposes of reducing HF risk cannot be recommended based on our results.”

Contributed by Kathi Head, ND


  • Stevens L, Linstead E, Hall J, Kao D. Association between coffee intake and incident of heart failure risk: a machine learning analysis of the FHS, the ARIC Study, and the CHS. Circ Heart Fail 2021 Feb;14(2):e006799. doi: 10.1161/CIRCHEARTFAILURE.119.006799.
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Higher vitamin C levels correlate with improved microvascular health 

Although vitamin C is well known for its role in preventing scurvy, its role in supporting blood vessel health is less well-known. The stability of very small blood vessels is readily detected in the gums as gingival bleeding, and in the retina, which can become prone to hemorrhage. Using the gums as surrogate markers, a meta-analysis of 15 controlled trials across six countries and including 1,140 participants investigated the correlation between vitamin C status and microvascular health. An additional 8,210 participants from the U.S.-based NHANES III study were included in the meta-analysis to also investigate the impact of vitamin C using retinal hemorrhage as an additional marker of microvascular health.

Supplementation with vitamin C (median 222 mg for 41 days) or increased dietary intake significantly reduced gingival bleeding in every study where participants began with low vitamin C blood levels (<28 μmol/L in six studies). However, this effect was limited when blood levels were higher (>48 μmol/L) prior to supplementation, or if gum health was maintained through other means, such as periodontal cleanings. In the NHANES III study, the tendency to have gingival or retinal bleeding was significantly higher in individuals who had low blood levels of vitamin C compared to those with higher blood levels.

The current recommendations for vitamin C intake are primarily based on the very low blood levels to prevent scurvy (11-28 μmol/L). The U.S. RDA recommendations vary between 15-155 mg/day. The authors suggest that sufficient evidence exists for the minimum recommended intake levels of vitamin C to be increased to provide support for healthy microvascular structure and other general health considerations.

Explore Thorne’s Vitamin C products

Contributed by Sheena Smith, MS MA 


  • Hujoel P, Kato T, Hujoel I, Hujoel M. Bleeding tendency and ascorbic acid requirements: systematic review and meta-analysis of clinical trials. Nutr Rev Published online February 1, 2021:nuaa115. doi:10.1093/nutrit/nuaa115
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Sun exposure and sex hormone levels – good or bad?

Because we know vitamin D is important for bone health, and sun exposure is an important way to maintain vitamin D levels, we might automatically assume that exposure to UV radiation from the sun is good for bone health. However, a new multi-center research study from Europe questions this assumption. Researchers from six European countries looked at the connection between UV exposure and levels of circulating sex hormones and gonadotropins.1

The study included 580 postmenopausal women who completed an interviewer-led questionnaire to assess lifestyle factors. Subjects also underwent hormone testing that included 17β-estradiol, estrone, estrone 3-sulfate, testosterone, and dehydroepiandrosterone sulfate (DHEA-S), as well as the gonadotropins follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin. In addition to the lifestyle questionnaire, which asked about sunscreen use and time spent outdoors, UV exposure was also estimated using satellite data from a European database.

The study found that higher exposure to UV radiation is associated with lower 17β-estradiol and estrone levels, as well as elevated FSH and LH levels. The researchers conclude that this could have a negative impact on bone health, as well as inflammation, hormone balance, cognitive function, wound healing, and overall biological aging.

This study is interesting because it may be the first of its kind to explore the relationship between sun exposure/behavior and global sex-hormone status. The researchers raise many interesting questions, and also point out that the relationship between UV exposure, vitamin D metabolism, and levels of sex hormones/gonadotropins is a complex one. (see simplified graphic here)

Despite the interesting findings, the study has several problematic features – some of which the researchers point out and others they do not. Those noted by the researchers include:

  1. The small number of non-white women in the cohort (so findings likely are not accurate for non-white women)
  2. No assessment of melatonin or shift work, which could contribute to understanding the hormonal picture; for example, higher melatonin levels may lower LH and vice versa.2
  3. No assessment of vitamin D status. Although a food frequency questionnaire evaluated dietary intake, there was no accounting for vitamin D supplementation and no assessment of vitamin D status by any laboratory method. This is critical because it is very possible that given the geography of the study, many women had low vitamin D despite any level of UV exposure. The prevalence of vitamin D insufficiency in postmenopausal European women has been shown to be close to 80 percent.3

Potential study problems not discussed include:

  1. Failure to discuss possible positive benefits of the findings. Most notably, lower levels of estrogens might be protective for some cancers, such as breast4 and colon.5
  2. No assessment of bone density or other markers that might support the presumption of a negative impact of lower circulating sex hormones. An assessment of n-telopeptide level or DEXA would have offered good support or helped to refute the primary findings. 

Overall, this study is interesting because it highlights the interconnected nature of environment, lifestyle, and hormone status in a geographically distributed group of postmenopausal women. However, given some of the weaknesses in the data, it seems premature to jump to conclusions about the impact of these findings.

Contributed by Jacqueline Jacques, ND


  1. Triebner K, Bifulco E, Barrera-Gómez J, et al. Ultraviolet radiation as a predictor of sex hormone levels in postmenopausal women: A European multi-center study (ECRHS). Maturitas 2021;145:49-55. doi:10.1016/j.maturitas.2020.12.011
  2. Kripke D, Kline L, Shadan F, et al. Melatonin effects on luteinizing hormone in postmenopausal women: a pilot clinical trial NCT00288262. BMC Womens Health 2006;6:8. doi:10.1186/1472-6874-6-8
  3. Bruyère O, Malaise O, Neuprez A, et al. Prevalence of vitamin D inadequacy in European postmenopausal women. Curr Med Res Opin 2007;23(8):1939-1944. doi:10.1185/030079907X219562
  4. Zhang X, Tworoger S, Eliassen A, Hankinson S. Postmenopausal plasma sex hormone levels and breast cancer risk over 20 years of follow-up. Breast Cancer Res Treat 2013;137(3):883-892. doi:10.1007/s10549-012-2391-z
  5. Murphy N, Strickler H, Stanczyk F, et al. A prospective evaluation of endogenous sex hormone levels and colorectal cancer risk in postmenopausal women. JNCI J Natl Cancer Inst 2015;107(djv210). doi:10.1093/jnci/djv210
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