How frequently can whole blood safely be donated?

 Maybe only twice a year for people who don't take iron supplements, according to this recent comment (on a randomized trial in the Netherlands).

Protecting the blood donor: ferritin-based intervals to improve donor health, by Laura Infanti, Lancet (online first) Published:June 13, 2024DOI:https://doi.org/10.1016/S0140-6736(24)01212-1

"Strict eligibility criteria and the ageing of the general population are among the main factors limiting blood donor availability,1 and render the retention of experienced donors and the acquisition of new volunteers a demanding task. Also, a temporary inability to give blood (eg, due to recent travel or a medical condition) can be a reason for abandoning blood donation permanently.2 Blood establishments are constantly making efforts to counteract blood shortages and the overall declining trends in donations.

"In this context, low haemoglobin concentration, which is the most common reason for donation deferral, is a key risk factor for the loss of active volunteers. Due to the loss of 220–250 mg of iron with each whole-blood donation, iron deficiency with or without anaemia is the most important side-effect of blood donation.

...

"A strong predictor of iron deficiency is the interval between donations. For healthy individuals not taking iron supplementation, recovering iron stores after the drawing of 450–500 mL of blood requires at least 180 days.6 Several observational studies questioned the minimal donation interval allowed by regulation as being too short for preventing iron deprivation,7 and the randomised INTERVAL study showed that shorter donation intervals, although increasing blood procurement, resulted in more frequent haemoglobin deferrals.8 Indeed, ensuring a sufficient blood supply and protecting healthy volunteers at the same time is very difficult. Thus, despite available evidence, European and US regulations permit whole-blood donations up to once every 56 days for both sexes, although at a maximum of six donations per year for male donors and four donations per year for female donors in Europe.

Here's the study itself:

• Meulenbeld A, 
• Ramondt S. 
• Sweegers MG
• , et al.

Effectiveness of ferritin-guided donation intervals in whole-blood donors in the Netherlands (FIND'EM): a stepped-wedge cluster-randomised trial.

Lancet. 2024; (published online June 13.)

https://doi.org/10.1016/S0140-6736(24)01085-7