New Vitamin D Study Conclusions are Misleading

VitalityExplorers.com

Dozens of media outlets are reporting on a new large Vitamin D study today. The study gave participants 2000 IUs of Vitamin D per day or a placebo for an average of about five years and investigated the risk of sustaining a fracture. (LeBoff et al New England Journal of Medicine, see reference below for more detail.)

Headlines like the ones below are circulating all over the internet.

• “Vitamin D Won’t Help Your Bones”

• “Study Finds Another Condition that Vitamin D Pills Don’t Help.”

Here is the conclusion from the paper:

“Vitamin D3 supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not selected for vitamin D deficiency, low bone mass, or osteoporosis.” (See Graph Below)

I think it is crucial to unpack the study and then let readers of Vitality Explorer News draw their own conclusions.

As a teaser, here is what I would have added to the conclusion of the paper:

Our study has a skewed ethnic demographic compared to 2020 United States data. Our study was also conducted in patients with an average age of 67.1 years old. We can only make conclusions based on the population we studied. Our results may not apply to younger patients or certain ethnic groups.

Here are the primary specifications of study:

• Number of Participants: 25,871

• Follow up: 5.3 years

• Mean Age: 67.1 years old

• 50.6% Women

Ethnic breakdown of the participants reported by the study:

• Black:  20.2%

• Hispanic: 4%

• Asian / Pacific Islander: 1.5%

• American Indian or Alaska Native:  0.9%

2020 data found the ethnic breakdown in the US (See reference below)

• Blacks:  12.6%

• Hispanic: 18.6%

• Asian:  5.9%

• American Indian or Alaska Native:  0.7%

The present study therefore included a higher percentage of Blacks and lower percentage of Hispanics and Asians.

The present study had 26.6% of people that identified as Black, Hispanic or Asian / Pacific Islander

US Demographic data from 2020 reports 37.8% of people that identify as Black, Hispanic or Asian / Pacific Islander.

The paper therefore contains significantly less people of color than is in the recently reported US population.

The paper reported baseline Vitamin D levels in only 65.5% of participants.

The reported adherence to the randomized protocol was 87.3% at 2 years and 85.4% at 5 years. This is excellent.

The paper, however, reported follow up Vitamin D levels on only 23.2% of participants and only 5.3% provided two year follow up blood data.

This is a significant flaw in the study. It is impossible to make meaningful conclusions with such low Vitamin D level follow up rates.

This was a difficult study to design and execute. The authors need to be congratulated about doing their best. The conclusions, however are far too broad for the data that was within study.

There are several questions that need to still be answered.

• Would the fracture rates be different if the population studied started supplementation in their 40s and continued for 20 years?

• What if they only included participants with a known vitamin D deficiency?

• Would the fracture rates be different if only Hispanic Asian populations were studied?

The study simply did not have enough of these groups to draw any meaningful conclusions.

The biggest flaw of the study is the lack of confirmation of Vitamin D levels. Only 5.3% had two year data. Call me a skeptic but I cannot draw any definitive conclusions on a dataset that has only five percent hard data follow up.

These are my personal opinions about this article. I believe the authors and the lay press are over-reaching with their conclusions. Please correct me if I made any mistakes on the data.

I welcome comments about this paper or my analysis of it.

(Disclaimer: I have been a reviewer for several elite medical journals for many years)

References:

Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults

LeBoff et al

BACKGROUND

Vitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent.

METHODS

In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D3 would result in a lower risk of fractures than placebo. VITAL was a two-by-two factorial, randomized, controlled trial that investigated whether supplemental vitamin D (2000 IU per day), n−3 fatty acids (1 g 3
per day), or both would prevent cancer and cardiovascular disease in men 50 years

of age or older and women 55 years of age or older in the United States. Participants were not recruited on the basis of vitamin D deficiency, low bone mass, or osteoporosis. Incident fractures were reported by participants on annual question- naires and adjudicated by centralized medical-record review. The primary end points were incident total, nonvertebral, and hip fractures. Proportional-hazards models were used to estimate the treatment effect in intention-to-treat analyses.

RESULTS

Among 25,871 participants (50.6% women [13,085 of 25,871] and 20.2% Black [5106 of 25,304]), we confirmed 1991 incident fractures in 1551 participants over a median follow-up of 5.3 years. Supplemental vitamin D3, as compared with placebo, did not have a significant effect on total fractures (which occurred in 769 of 12,927 participants in the vitamin D group and in 782 of 12,944 participants in the placebo group; hazard ratio, 0.98; 95% confidence interval [CI], 0.89 to 1.08; P=0.70), nonvertebral fractures (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P=0.50), or hip fractures (hazard ratio, 1.01; 95% CI, 0.70 to 1.47; P=0.96). There was no modification of the treatment effect according to baseline characteristics, including age, sex, race or ethnic group, body-mass index, or serum 25-hydroxyvitamin D levels. There were no substantial between-group differences in adverse events as assessed in the parent trial.

CONCLUSIONS

Vitamin D3 supplementation did not result in a significantly lower risk of fractures than placebo among generally healthy midlife and older adults who were not se- lected for vitamin D deficiency, low bone mass, or osteoporosis. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; VITAL ClinicalTrials.gov number, NCT01704859.)

Other References:

https://www.channel3000.com/i/vitamin-d-supplements-wont-help-your-bones-large-study-finds/

https://www.nytimes.com/2022/07/27/health/vitamin-d-bone-fractures.html