This is an area that I became aware of a decade ago and used this knowledge to discard some suggestions and take other suggestions based on the physical characteristics of the brain. This has major implication for brain fog, autism, ME/CFS, depression, Alzheimer’s, Long Haul Covid and many many more conditions.

The literature

“Research on disease-modifying treatments for  central nervous system  [CNS] diseases have generated a cemetery of failed drugs, rejected in part because of their incapacity to cross the BBB” [3,4,5,6,7]. 

The Molecular Weight [MW] threshold of BBB drug transport of small molecules has been demonstrated previously in studies of drug penetration into the brain.^33, 34 Blood–brain barrier permeation decreases 100-fold when the size of the drug is increased from an MW of 300 Da, which corresponds to a surface area of 50 square angstroms, to an MW of 450 Da, which corresponds to a surface area of 100 square angstroms.³⁵

Drug transport across the blood–brain barrier [2012]

• Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level [2021] Hints that some infections/conditions may drop the threshold lower.
• Low Molecular Weight (poly)Phenol Metabolites Across the Blood-Brain Barrier: The Underexplored Journey [2021]

I remember that for my treatment of ME/CFS back in 2000, Low Molecular Weight Heparin was what was advocated. It was found far more effective than normal heparin (and costed 30+time more!!)

Getting information on Molecular Weight

What is Da? It’s Dalton — “Measure of molecular weight or molecular mass. One molecular hydrogen molecular atom has molecular mass of 1 Da, so 1 Da = 1 g/mol.” This information is often available on Wikipedia in the left hand column as molecular mass. i.e. 457.483 g·mol⁻¹ –> 457 Da

Information is also available at https://pubchem.ncbi.nlm.nih.gov/

If there is a choice, you want the smallest number. Remember we are talking 100x LESS getting thru with an increase of weight by 50%! Some examples:

• Piracetam: 142.16 g/mol – this has always been an excellent removal of brain fog for me!
• Niacin: 123.11 g/mol — also helps me with brain fog
• Vitamin C: 176.12 g/mol
• alpha-Lipoic acid: 206.3 g/mol
• Quercetin: 302.23 g/mol
• Curcumin: 368.4 g/mol
• Vitamin D: 384.6 g/mol
• Rutin: 610g/mol
• Heparin (compound): 1134.9 g/mol – hence why low molecular weight heparin worked better!
• Cyanocobalamin (Vitamin B12): 1355.4 g/mol — would not expect any impact on cognitive issues
• Antibiotics:
  • Tetracycline: 444.4 g.mol
  • Doxycycline: 444.4 g.mol
  • Minocycline: 457.5 g/mol
  • Azithromycin: 749 g/mol
  • Vancomycin 1449.2 g/mol

Bottom Line

The concept of “needing to take anti-inflammatories for brain inflammation” is correct — the gotcha is that many of the items you may take will never reach the brain because they are too big! Go thru your lists (and suggestions from others) and trim them down to the light molecular weight ones. You will likely get much better success — I did!