Research news articles are produced to keep practitioners up to date on impactful research that is relevant to the field of integrative medicine.
In this research update, we will discuss two recent studies that have been making waves in the news.
Are dietary supplements ineffective in lowering LDL? (November 2022)
Heart disease is the leading cause of death in the United States, and coronary artery disease is the most common type of cardiovascular disease. (2) Dietary supplements for dyslipidemia are often used with or in place of prescription medication as they are often considered safer and just as effective as statins.
The authors of this randomized, placebo-controlled, parallel-arm trial sought to determine the effectiveness of six commonly prescribed dietary supplements on serum low-density lipoprotein (LDL) compared to low-dose rosuvastatin and placebo.
190 participants between the ages of 40 and 75 were randomized to one of eight possible study groups for 28 days. Formal blinding was not undertaken because supplements varied in size, shape, and dose (number of capsules or tablets per day). The study groups included:
- 5 mg of rosuvastatin
- 2,400 mg of fish oil
- 2,400 mg of cinnamon
- 5,000 mcg allicin
- 4,500 mg of curcumin with bioperine
- 1,600 mg of plant sterols
- 2,400 mg of red yeast rice
The authors of the study found the following:
- Low-dose rosuvastatin significantly decreased serum total cholesterol, LDL, and triglyceride levels compared to the placebo and dietary supplement groups.
- None of the dietary supplement groups significantly decreased LDL compared to the placebo group.
- Adverse effects were minimal in all groups. (4)
It’s important to keep the following in mind when reviewing the results of this study. First, this study was supported by an unrestricted grant from AstraZeneca, which is the manufacturer of the brand name for rosuvastatin, Crestor.
Although supplements can play an important role in preventing or treating cardiovascular disease, in many cases, they are not “powerful” enough to produce the same fast-acting results as prescription medications. Consequently, the short duration of the trial may explain why participants in the dietary supplement groups did not experience any benefit. From clinical experience, Dr. Jeff Gladd, MD, Fullscript’s chief medical officer, explains that cholesterol-lowering supplements often require 90 days or longer to be effective. (1)(3)(6)(7)(8)(9)
Does nicotinamide riboside cause cancer? (January 2023)
Nicotinamide riboside (NR), a form of vitamin B3 and a precursor to NAD+, has been shown to have various beneficial therapeutic effects on metabolic, cardiovascular, and neurological disorders. However, many aspects of the physiological uptake of NR in mammals remain unclear, especially in cancer cells.
The authors first studied the uptake of NR in seven different types of cultured cancer cells using a novel bioluminescent-based NR (BiNR) probe. Briefly, the cancer cells were incubated with a reagent that produces visible light when mixed with azido-modified nicotinamide riboside (AzNR). The degree of bioluminescence was proportional to the amount of AzNR taken up by the cells.
Out of the seven cultured cancer cells, MDA-MB-231 cells, which cause a highly aggressive triple-negative breast cancer (TNBC), had the highest update of NR. These cells were then used for the following two in vivo studies.
In the first in vivo study, a total of 19 mice were fed either an NR-enriched diet (n=10) or a standard chow diet (n=9) for two weeks. The mice were then injected under the skin with MDA-MB-231 cells. The authors then monitored the mice to determine the prevalence of tumors in both groups.
Similarly to the first in vivo study, mice in the second study were also fed either an NR-enriched diet (n=11) or a standard chow diet (n=12) for two weeks. However, the MDA-MB-231 cells were injected directly into their hearts. The authors then monitored the mice to determine the rate of metastasis in both groups.
In the first study, 70% of the mice fed an NR-enriched diet compared to 55% of the mice fed a standard chow diet developed detectable tumors ten weeks after having MDA-MB-231 cells injected under their skin.
In the second study, brain metastases were detected in 81% of the mice fed an NR-enriched diet compared to 25% of the mice fed a standard chow diet after being injected into the heart with MDA-MB-231 cells.
The authors concluded that NR supplementation significantly increases the prevalence of cancer and the rate of metastases to the brain. Although the exact mechanism is unknown, they suspect that NR supplementation may enhance the metastatic potential of cancer cells and/or decrease the integrity of the blood-brain barrier leading to preferential invasion of the brain by cancer cells. (5)
There is some debate regarding the clinical relevance of this study as it was conducted on a small sample of cultured human cancer cells and mice. Currently, there are no human clinical trials investigating the possible cancer-promoting effects of NR.
However, as the authors explain, these results demonstrate the importance of personalized medicine. In other words, NR supplementation may be, for example, beneficial for some with cardiovascular disease but inappropriate for others with a significant personal or family history of cancer.
- Askari, F., Rashidkhani, B., & Hekmatdoost, A. (2014). Cinnamon may have therapeutic benefits on lipid profile, liver enzymes, insulin resistance, and high-sensitivity C-reactive protein in nonalcoholic fatty liver disease patients. Nutrition Research , 34(2), 143–148. https://doi.org/10.1016/j.nutres.2013.11.005
- CDC. (2022, September 1). Heart Disease. Centers for Disease Control and Prevention. https://www.cdc.gov/heartdisease/index.htm
- Jamilian, M., Foroozanfard, F., Kavossian, E., Aghadavod, E., Shafabakhsh, R., Hoseini, A., & Asemi, Z. (2020). Effects of curcumin on body weight, glycemic control and serum lipids in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Clinical Nutrition ESPEN, 36, 128–133. https://doi.org/10.1016/j.clnesp.2020.01.005
- Laffin, L. J., Bruemmer, D., Garcia, M., Brennan, D. M., McErlean, E., Jacoby, D. S., Michos, E. D., Ridker, P. M., Wang, T. Y., Watson, K. E., Hutchinson, H. G., & Nissen, S. E. (2022). Comparative effects of low-dose Rosuvastatin, placebo and dietary supplements on lipids and inflammatory biomarkers. Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2022.10.013
- Maric, T., Bazhin, A., Khodakivskyi, P., Mikhaylov, G., Solodnikova, E., Yevtodiyenko, A., Giordano Attianese, G. M. P., Coukos, G., Irving, M., Joffraud, M., Cantó, C., & Goun, E. (2023). A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism. Biosensors & Bioelectronics, 220, 114826. https://doi.org/10.1016/j.bios.2022.114826
- Trautwein, E. A., Koppenol, W. P., de Jong, A., Hiemstra, H., Vermeer, M. A., Noakes, M., & Luscombe-Marsh, N. D. (2018). Plant sterols lower LDL-cholesterol and triglycerides in dyslipidemic individuals with or at risk of developing type 2 diabetes: A randomized, double-blind, placebo-controlled study. Nutrition & Diabetes, 8(1), 30. https://doi.org/10.1038/s41387-018-0039-8
- Verhoeven, V., Van der Auwera, A., Van Gaal, L., Remmen, R., Apers, S., Stalpaert, M., Wens, J., & Hermans, N. (2015). Can red yeast rice and olive extract improve lipid profile and cardiovascular risk in metabolic syndrome?: A double blind, placebo controlled randomized trial. BMC Complementary and Alternative Medicine, 15, 52. https://doi.org/10.1186/s12906-015-0576-9
- Yang, Y.-S., Su, Y.-F., Yang, H.-W., Lee, Y.-H., Chou, J. I., & Ueng, K.-C. (2014). Lipid-lowering effects of curcumin in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled trial. Phytotherapy Research, 28(12), 1770–1777. https://doi.org/10.1002/ptr.5197
- Zadhoush, R., Alavi-Naeini, A., Feizi, A., Naghshineh, E., & Ghazvini, M. R. (2021). The effect of garlic (Allium sativum) supplementation on the lipid parameters and blood pressure levels in women with polycystic ovary syndrome: A randomized controlled trial. Phytotherapy Research, 35(11), 6335–6342. https://doi.org/10.1002/ptr.7282