Let’s first take a look at Vitamin B12:
Vitamin B12 can exist in different forms, and not all forms are biologically active. Around 20% of Vitamin B12 in the blood is bound to transcobalamin. In this bound form, it is called holotranscobalamin (HoloTC). HoloTC is the active form of Vitamin B12. It can be taken up by all cells through specific receptors.
The remaining approximately 80% of Vitamin B12 is bound to the protein haptocorrin. This complex is considered biologically inactive because only liver cells have the appropriate receptors for uptake.
Which tests are suitable for assessing Vitamin B12 status?
Many people in the Facebook group report that doctors often measure total Vitamin B12 in blood serum as the standard test. This is probably because some physicians are simply unaware that much more informative testing methods are now available.
Total Vitamin B12 in Blood Serum
This test measures both inactive and active forms of Vitamin B12—essentially everything circulating in the bloodstream. However, only the active forms are metabolically relevant because only they can enter cells and influence metabolic processes. Therefore, total serum Vitamin B12 has the lowest diagnostic value of all available testing methods.
Holo-TC in Blood Serum
Measuring Holo-TC levels in blood serum is significantly more accurate because it specifically detects biologically available Vitamin B12. If Holo-TC levels are low, it suggests that the body may not have enough usable Vitamin B12 and may already be drawing from its stored reserves. Holo-TC is therefore considered an early marker of Vitamin B12 deficiency.
Is Enough Vitamin B12 Reaching the Cells?
Vitamin B12 is an essential cofactor for various enzymes involved in numerous metabolic processes. To determine whether sufficient Vitamin B12 is reaching the cells and performing its metabolic functions, it is also possible to measure the byproducts of B12-dependent metabolic pathways.
Measuring Methylmalonic Acid (MMA)
In the body, methylmalonyl-CoA is converted into succinyl-CoA. Vitamin B12 is absolutely essential for this process. If sufficient B12 is not available, methylmalonic acid is produced. This can be measured in both blood and urine and serves as an indirect marker of Vitamin B12 deficiency. However, this test only detects deficiencies once metabolic disturbances have already occurred. Combined with the Holo-TC measurement, it provides the highest diagnostic value.
A home test can be ordered from the Medivere laboratory. Use the code AP36312 to receive a 5% discount.
Measuring Biologically Active Vitamin B12 in the Blood
Chemically, Vitamin B12 exists in three different forms:
- Cyanocobalamin (biologically inactive),
- Adenosylcobalamin (biologically active),
- Methylcobalamin (biologically active).
The biologically active forms can be measured directly in the blood. An explanation of how this works can be found here.
Testing Vitamin B6
Vitamin B6 is not a single vitamin but rather a collective term for six different chemical forms in which Vitamin B6 can occur:
- Pyridoxal (PL),
- Pyridoxine (PN),
- Pyridoxamine (PM),
- Pyridoxal-5-phosphate (P5P),
- Pyridoxine-5-phosphate (PNP),
- Pyridoxamine-5-phosphate (PMP),
- 4-Pyridoxic Acid.
P5P is considered the active form of Vitamin B6 that can function inside cells and influence metabolism. Whether the ratio of the other Vitamin B6 forms affects P5P activity in people with HPU is currently being investigated.
Standard Vitamin B6 testing measures levels in blood serum. However, this method cannot distinguish between active and inactive Vitamin B6 metabolites. This can be particularly problematic for people with HPU because some individuals are unable to convert inactive forms of Vitamin B6 into the active form (P5P). In such cases, serum Vitamin B6 levels may appear high even though the cells are deficient in P5P.
To overcome this issue, the following solution is recommended:
Measure the Active Form of Vitamin B6
This blood test uses bacteria that can grow only in the presence of P5P. As a result, the test specifically measures the metabolically active form of Vitamin B6.
Conclusion from Dr. von Baehr of IMD Berlin: “It is important not to measure B6 or B12 in serum simply as a total quantity. Unfortunately, this is still done far too often. Particularly in HPU patients, a Vitamin B6 deficiency can only be detected through a bioactivity test and not through the total amount present in blood serum.”
The active Vitamin B6 test can be ordered by both private individuals and practitioners here. IMD offers a courier service in Germany, Austria, and Switzerland that collects samples and delivers them to the laboratory within one day. The Biovis laboratory also offers bioactive Vitamin B6 testing using bacteria. However, with Biovis, testing can only be ordered through healthcare practitioners.
Connect with Other People Affected by HPU:
Not yet a member of the HPUandYou Facebook Group? You can join here and connect with other people living with HPU: https://www.facebook.com/groups/hpuandyou