Thread by @RAKresser

1/x I awoke today to multiple messages asking me for my take on the SPORT ("Supplements, Placebo, or Rosuvastatin Study") study presented at #AHA2022.

My take - sterol and red yeast rice arms have issues around underpowering, small dosage size, and lack of supplement testing.

Interested to hear others' takes:

@Drlipid @drpablocorral @ErinMichos @ljlaffin @DBelardoMD @pabeda1 @maciejbanach @DrNadolsky #CardioTwitter @afgcicero

2/x The study investigated:

- 5mg of rosuvastatin
- 2,400mg of fish oil
- 2,400mg of cinnamon
- 5,000mcg of garlic
- 4,500mg of turmeric
- 1,600mg of plant sterols
-2,400mg of red yeast rice

Public link to the abstract is here 👇
jacc.org/doi/10.1016/j.…

3/x The study found that:

- rosuvastatin lowered LDL by 37.9%
- fish oil lowered LDL by 3.4%
- cinnamon raised LDL by 0.4%
- garlic raised LDL by 5.1%
- turmeric lowered LDL by 1.3%
- plant sterols lowered LDL by 4.4%
- red yeast rice lowered LDL by 6.6%

4/x The plant sterols and red yeast rice were the most effective supplements at lowering LDL cholesterol in the study.

In a 2014 meta-analysis, 600-3,300 mg of plant sterols was associated with LDL lowering of 6-12%: pubmed.ncbi.nlm.nih.gov/24780090/

6/x The expected LDL lowering of 1,600mg of plant sterols is ~6% based on the dose-dependence chart from the above meta-analysis.

In SPORT plant sterols only lowered LDL by 4.4%, with a 95% confidence of 8.7% - 0.1% LDL lowering. So - slight underperformance by plant sterols.

7/x The "proposed tweet" from the paper includes "supplements no different from placebo." Wrt plant sterols this overstates the findings. The study was powered to be significant with a 15% LDL-lowering, when plant sterols at the chosen dose could only be expected to deliver 6%.

8/x So, one would not expect a statistically significant difference from placebo given the study size. And indeed, plant sterols lowered LDL cholesterol more than placebo but not by a statistically significant amount.

9/x Red yeast rice's underperformance was more striking. Red yeast rice can be expected to lower LDL-cholesterol by ~40mg/dl (or roughly 33% at the RYR group's baseline LDL) with a monacolin K dose of 10.4mg/dl per this 6,663 patient meta-analysis: atherosclerosis-journal.com/article/S0021-…

10/x Importantly, each study in this meta-analysis, as well as more recent studies such as @afgcicero , 2017, below **tested the amount of monacolin K (the active ingredient)** in the red yeast rice they studied.

ncbi.nlm.nih.gov/pmc/articles/P…

11/x It appears the SPORT authors did not test for monacolin K in the red yeast rice. This is strange in light of the authors' own statement that for red yeast rice "different product formulations and manufacturers can result in varying levels of efficacy, or lack thereof"

12/x The authors' findings likely demonstrate that they chose a brand of red yeast rice containing little monacolin K, purposely or accidentally. Without the monacolin K testing one cannot compare this to the tens of thousands of other patients treated with red yeast rice.

13/x In conclusion -- I think the studies findings are likely accurate as to garlic, cinnamon, fish oil and turmeric. With regard to plant sterols they chose a small dose, got slight underperformance, and didn't power the study to find a significant difference.

14/x With regard to red yeast rice, the authors likely chose a brand containing little active ingredient for reasons known only to them, and so comparison to the large set of known red yeast rice studies is impossible.

15/x I would ask the authors to append to their final article the test results for monacolin K from any remaining batches of red yeast rice used in the study to try to give the medical and scientific community the context by which to understand the result.

16/17 I am not unbiased in this debate. My company, ZIZI, has created a once-daily, 80 calorie supplement bar containing 2.4grams of red yeast rice and 2.0grams of plant sterols. We launch February 2023 -- if you are interested you can join the waitlist at zizi.co

17/17 Any reporters who are interested in getting more context around this study please reach out, my DMs are open