The first time I became aware that elevated hemoglobin A1c was working in clinic. We had a coworker who ate a low carbohydrate diet, exercised regularly, but had chronic and persistent elevated hemoglobin A1c. Unfortunately, at the time I did not know what I do now, so I could not help her look for reasons why. The other medical staff pointed to additional, obscure labs that could confirm or deny that this was indicative of true diabetes, but that single lab number gave her great grief and drove her to drive her carbs lower and exercise more – to no avail! It became apparent that this was not a lifestyle driven cause, but her concern over her future risk was not abated. Knowing what I know now, I would have given her the following information I am about to share with you.
More recently, I had a new client come in who has noticed her hemoglobin A1c creeping up after menopause. This is all too common! There are a number of reasons why this occurs which I will speak to, but she was concerned about this especially as she has an active job, eats an unprocessed whole foods diet, and avoids excessive alcohol and sweets. She is the poster child for healthy living! While there have been some changes that can increase her risk (menopause being one of them) I also saw in her initial labs that there may be nutritional factors outside of her carbohydrate or sugar intake that may be giving her an exaggerated reading. While we wait for newer labs to confirm or deny my suspicions, I thought I’d share what I will be telling her here, because nuance is everything and I expect – especially with the use of GLP-1s – that we may see more unexplained cases of elevated hemoglobin A1c in the future that may be chalked up to genetics and leave people fearful for a future of diabetes they cannot control, rather than an understanding of the usefulness and shortcomings of hemoglobin A1c.
What is Hemoglobin A1c, Anyway?
Every red blood cell (RBC) in your body is packed with hemoglobin, the protein that carries oxygen from your lungs to all the tissues in your body. As those cells circulate, glucose that is also in your bloodstream drifts into them and sticks to the hemoglobin. This is called glycation, and it’s basically what it sounds like: your hemoglobin slowly gets sugar-coated. The more glucose floating around, the more coating builds up. Hemoglobin A1c is simply the percentage of your hemoglobin that has picked up that sugar coat.
The clincher here is that a red blood cell lives, on average, 120 days. This is where the 3 month average glucose level gets estimated from your Hemoglobin A1c! It’s not perfect, as the last few weeks matter more than what happened 10 weeks ago, but it’s as close as we’ve got.
The diagnostic ranges look like this:
- Below 5.7%: normal
- 5.7–6.4%: prediabetes
- 6.5% and above: diabetes
If you’ve already landed in that middle range, How to Reverse Prediabetes and Age Like a Boss walks you through what to do about it.
A really important aspect to this though, is the assumption that our RBCs live 120 days. A1c depends on how long your red blood cells live. Glucose exposure matters. But so does time. An older population of red blood cells has had more days to collect sugar, even if your blood sugar never budged. Hold onto that little fact for a moment while I move on….
Hemoglobin A1c is Still Awesome!
Despite everything else that I am going to say next, Hemoglobin A1c is still a fantastic test, and highly reliable. In the vast majority of people, an elevated A1c means exactly what it looks like: blood sugar has been running high. It’s a validated marker for prediabetes and diabetes, and and it doesn’t require fasting. It isn’t thrown off by one bad night of sleep or a birthday cake.
This is why doctors love it and why patients increasingly ask for it by name. Keep in mind, over the last 10 years, I have only seen 2 people for whom this has not been a reliable indicator that glucose has been chronically elevated. If I had stayed in that high volume medical practice the last 3 years I may have seen 1 or 2 more cases, but I highly doubt it would be more than that.
So here’s my rule of thumb: If your A1c is high, assume it’s telling the truth until proven otherwise. Everything that follows in this post is a reason to investigate further is you see idiosyncracies, not a reason to ignore a number you don’t like!
If your Hemoglobin A1c is elevated, be concerned but don’t panic. Prediabetes is highly responsive to nutrition and lifestyle changes, and this post is where I’d start.
Why It Matters If Your HemoglobinA1c is a False Flag
The hemoglobin A1c often becomes a decision point for you and your doctor, which is why I am bothering to make a post about potentially misleading readings.
An A1c of 6.5% or higher, confirmed by a second abnormal result, is enough for a diabetes diagnosis (1) [ADA]. That diagnosis goes onto insurance paperwork and into your medical chart, and it can bring a prescription for metformin or a GLP-1. For someone whose blood sugar is genuinely high, those are valuable tools. For someone whose A1c is inflated other reasons, they get treated for a problem they actually do not have while the real one keeps going unaddressed.
Then there’s the emotional strain and worry over a single lab marker. Plenty of people I work with are eating well, moving daily, and still see their A1c or their weight or their cholesterol creep up. They often blame themselves. Sometimes their lifestyle is the factor, sometimes their body has changed and it requires new habits to rebalance, and sometimes, albeit rarely, the number is the thing that’s off and it has nothing to do with them!
Because blood sugar is tightly tied to cardiovascular risk, which I covered here, it is important that our labs to be telling a true picture, and that involves looking at the full picture.
A quick note: While a Hemoglobin A1c can also read falsely low, that’s uncommon in the general population and a topic for another post.
When Your Nutrient Status Misleads Your Doctor
Let’s go back to that bit of trivia about the life of a red blood cell. Bring it back into consciousness, because it’s the smoking gun. Our bone marrow continuously builds new red blood cells to replace the old ones after they’ve been around about 120 days. This RBC production factory needs raw materials. Those raw materials are made up of …. vitamins and minerals!
If your supply of raw materials falls short, production slows. Slowed RBC production means existing cells hang around longer, collect more sugar, and …. you guessed it! Your A1c climbs, even if your blood sugar hasn’t changed at all. Here are the nutrients most strongly correlated with elevated hemoglobin A1c:
Iron
Iron is the most common nutrient deficiency in the world, and the best-documented non-glucose cause for an elevated A1c, based upon existing research. Without enough iron, you can’t build hemoglobin, and without hemoglobin, you can’t build red blood cells. So the cells you already have age beyond their ideal lifespan.
The evidence runs both directions, which is what makes it convincing. Iron deficiency is associated with higher A1c in people without diabetes, and correcting the deficiency brings A1c back down (2,3). It’s important to know that you don’t have to be anemic for this to matter! Low iron stores can show up on a ferritin test before your hemoglobin drops. But if nobody’s checked your ferritin, nobody knows.
B12 and Folate
These two build the DNA that every new red blood cell needs. Without them, the bone marrow turns out fewer, larger, clumsier cells (a condition called megaloblastic anemia, if you want the clinical term). Fewer new cells lead to an older population and more sugar-coating on those older cells.
To keep your RBC factory stocked with raw materials, you want a diet rich in heme iron and B12. This is most abundant and best absorbed from animal foods like red meat, lamb, shellfish, and liver. Animal-free folks will have a harder time of it, and may need to supplement. Plant sources of iron such as beans and spinach are not as well absorbed, but vitamin C rich foods eaten with them can help combat this.
Vitamin D
While low vitamin D is associated with higher A1c, these studies have been observational, and supplementation trials have yielded mixed results. Some research also suggests the impact may be more significant in women than men, but that was just one study, so don’t draw any conclusions! The most likely explanation for this association is that vitamin D influences insulin sensitivity. That’s a real effect on glucose metabolism rather than a shortcoming of testing. It’s worth checking Vitamin D status, as it also impacts immune regulation, mood, and bone health in addition to metabolic health (4,5)
Magnesium, Zinc, and Chromium
These matter for blood sugar too. But they act on how your body actually handles glucose, not on red blood cell lifespan. If they’re low, your A1c is likely telling the truth. The good news is that correcting these deficiencies can bring down your A1c by making your cells more receptive to insulin and better able to process glucose. For the full rundown, listen to Which Nutrients Are Needed for Blood Sugar Regulation?.
Medications Side Effects Your Pharmacist Forgot to Mention
First, it’s important to know that some medications genuinely raise blood sugar. Your A1c isn’t lying about those; it’s reporting accurately. The list includes corticosteroids like prednisone, thiazide diuretics, certain antipsychotics like olanzapine and clozapine, the transplant drug tacrolimus, niacin, and, to a small degree, statins. If you take any of these and your A1c has crept up, that’s worth discussing with your prescribing physician. It goes without saying (but I must in this litigious society) that you should never stop a prescribed medication without speaking to your doc. You and your doctor can discuss the benefits and drawbacks of your unique situation, and perhaps find alternatives if it is deemed wise to do so.
Then, there are the medications that raise A1c without touching your blood sugar. They do it in two ways:
Route 1: Depleting your nutrient stores
Many common medications quietly deplete the very nutrients your bone marrow needs.
- Metformin lowers B12 absorption over time (6). Yes, the drug prescribed to lower your A1c can nudge it back up through B12 depletion. The irony isn’t lost on me. B12 monitoring is recommended for long-term metformin users (7), so if you’re on it, ask whether yours has been checked.
- Acid blockers, both proton pump inhibitors (omeprazole, pantoprazole) and H2 blockers (famotidine), reduce the stomach acid you need to absorb B12 and iron. It also inhibits calcium and magnesium absorption, increasing risk of osteoporosis (8). Millions of people take these for years, thinking they are as benign as aspirin.
- Methotrexate, trimethoprim, and some anti-seizure medications interfere with folate (9-11).
Route 2: Throwing off the test with high-dose aspirin
This one is pure chemistry. Aspirin’s chemical name is acetylsalicylic acid. In your body, it hands off a small chemical tag called an acetyl group, which can stick to hemoglobin. When glucose sticks to hemoglobin, it changes the protein’s electrical charge. Aspirin’s tag changes it in a similar way.
Some lab methods, particularly older ones, measure A1c by sorting hemoglobin according to its charge. They can’t tell the two tags apart. Aspirin-tagged hemoglobin gets counted as sugar-tagged, and your A1c reads higher than your blood sugar actually was. Think of a vending machine that identifies coins by weight. Slip in a washer that weighs the same as a quarter, and it’ll happily count it as a quarter.
Before you toss your daily baby aspirin: this is a concern at high, anti-inflammatory doses (grams per day), not low-dose therapy. Most modern certified lab methods are largely unaffected, but it would be wise, when going in to get labs, to mention to the lab techs if you are taking high doses of aspirin. (12)
Hypothyroidism and Other Conditions
Hypothyroidism
Your thyroid sets the pace for nearly everything in your body, including how quickly you make new red blood cells. When thyroid hormone runs low, production slows, and you know the rest by now: older cells, more sugar-coating, higher A1c. The strongest evidence comes from treatment. In people with hypothyroidism but without diabetes, A1c drops after starting thyroid hormones, even though glucose doesn’t change. Blood sugar stays the same, but hemoglobin A1c drops because those old red blood cells are starting to be replaced more rapidly.
Thyroid issues also rarely travel alone. Hashimoto’s, the autoimmune form, is linked to other autoimmune conditions that impair B12 and iron absorption. So a sluggish thyroid can raise A1c directly and by draining the nutrients mentioned earlier. If you have thyroid disease, make sure to get labs once or twice a year to ensure TSH stays within range and other markers like cholesterol and hemoglobin A1c are not creeping up due to insufficient treatment!
Other conditions that can inflate A1c
- Spleen Removal. Your spleen normally clears out aging red blood cells. After a splenectomy, those cells stick around longer, and A1c rises accordingly.
- Kidney disease. A chemical byproduct called carbamylated hemoglobin can interfere with some tests and push results up. Meanwhile, the anemia and medications common in kidney disease push them down. The net effect is unpredictable, which makes A1c less trustworthy here.
- Hemoglobin variants. Sickle cell trait and other inherited variants can throw off certain A1c methods, in either direction depending on the test. Many people carry sickle cell trait without knowing it. If your lab knows you carry a variant, it can use a method that isn’t affected.
- Heavy alcohol use. Alcohol byproducts may interfere with some assays, and chronic drinking depletes folate.
- Very high bilirubin. This has been reported to interfere with certain tests.
Your doctor is likely to know and understand the impact these conditions have on hemoglobin A1c. You may find that they order other labs in addition to glucose, like insulin or HOM-IR. Or they may tell you not to worry about an increased Hemoglobin A1c, because they know not to be concerned, but don’t always take the time to explain why to you. If you are a heavy drinker, consider seeking support to reduce or eliminate alcohol (there are now great medications available in addition to long-standing support groups), as chronic high alcohol consumption causes a whole host of problems beyond elevated A1c.
Resources:
- Hardikar, P. S., Joshi, S. M., Bhat, D., Raut, D., Katre, P. A., Lubree, H., Jere, A., Pandit, A., Fall, C., & Yajnik, C. (2012). Spuriously High Prevalence of Prediabetes Diagnosed by HbA1c in Young Indians Partly Explained by Hematological Factors and Iron Deficiency Anemia. Diabetes Care, 35, 797 – 802. https://doi.org/10.2337/dc11-1321
- Kim, C., Bullard, K., Herman, W., & Beckles, G. (2010). Association Between Iron Deficiency and A1C Levels Among Adults Without Diabetes in the National Health and Nutrition Examination Survey, 1999–2006. Diabetes Care, 33, 780 – 785. https://doi.org/10.2337/dc09-0836
- Zhao, H., Zhen, Y.-F., Wang, Z., Qi, L., Li, Y., Ren, L.-P., & Chen, S.-C. (2020). The Relationship Between Vitamin D Deficiency and Glycated Hemoglobin Levels in Patients with Type 2 Diabetes Mellitus. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 13, 3899 – 3907. https://doi.org/10.2147/dmso.s275673
- Mangal, D., Shaikh, N., Tolani, H., Pandey, A., Gautam, D., Gupta, S., Kalra, S., Sharma, K. C., Prasad, J., Tewari, R., & Anwar, F. (2025). A systematic review and meta-analysis to assess the effect of hidden hunger on glycaemic control in patients with type 2 diabetes. Scientific Reports, 16. https://doi.org/10.1038/s41598-025-31681-z
- Tiwari, A., Singh, R. K., Satone, P. D., & Meshram, R. J. (2023). Metformin-Induced Vitamin B12 Deficiency in Patients With Type-2 Diabetes Mellitus. Cureus, 15. https://doi.org/10.7759/cureus.47771
- RONAK D. GHIYA, MAYA FAYFMAN; 131-LB: Prevalence of Vitamin B12–Monitoring among Patients Receiving Metformin in a Public Hospital. Diabetes 1 June 2022; 71 (Supplement_1): 131–LB. https://doi.org/10.2337/db22-131-LB
- Nafea, S., Iguh, C., Waseem, F., Babar, T., Masood, M. H., Ali, M. A., Qasem, H., & Atoom, G. I. (2026). Association of Long-Term Proton Pump Inhibitor Use With Nutrient Deficiencies: A Retrospective Cross-Sectional Study. Cureus, 18. https://doi.org/10.7759/cureus.106137
- Pathak, S. (2025). Fatal Flaw in the Folate Pathway: Methotrexate-Bactrim Interaction, Misleading Levels, and a Cautionary Case. Cureus, 17. https://doi.org/10.7759/cureus.99984
- Petersen, K. M., Eplov, K., Nielsen, T. K., Jimenez-Solem, E., Petersen, M., Broedbaek, K., Popik, S. D., Hansen, L. K., Poulsen, H. E., & Andersen, J. T. (2016). The Effect of Trimethoprim on Serum Folate Levels in Humans: A Randomized, Double-Blind, Placebo-Controlled Trial. American Journal of Therapeutics, 23, e382–e387. https://doi.org/10.1097/mjt.0000000000000372
- Reynolds, E. H. (2024). Antiepileptic drugs, folate one‐carbon metabolism, genetics, and epigenetics: Congenital, developmental, and neuropsychological risks and antiepileptic action. Epilepsia, 65, 3469 – 3473. https://doi.org/10.1111/epi.18120
- Gils, C., Reinholdt, B., Andreassen, B. D., Brandslund, I., & Vinholt, P. (2018). False increase of glycated hemoglobin due to aspirin interference in Tosoh G8 analyzer. Clinical Chemistry and Laboratory Medicine (CCLM), 56, e118 – e120. https://doi.org/10.1515/cclm-2017-0768
