When Prenatal B6 Backfires: How Morning Sickness Supplements Can Paradoxically Make You More Tired
70–80% of pregnant women experience the nausea and/or vomiting of morning sickness, with the severe form—hyperemesis gravidarum—affecting as many as 1 in 50.
B6 is very commonly prescribed worldwide for such morning sickness. It’s considered by many doctors and regulatory agencies to be the first-line agent, often prescribed as a mixed B6 + doxylamine and in dosages often up to 100 mg per day total.
ACOG, for example—a major medical regulatory agency—recommends 10-25 mg B6 three to four times daily, taking you close to that 100 mg per day.
That’s a lot of B6.
And yes, it helps a lot of people. Symptomatically, most women can achieve some degree of pregnancy nausea relief via B6 alone. And if that saves them from having to go to the hospital and/or take riskier, second-line medications, that’s of course great.
But the problem is that B6 has its risks.
The Risks of B6
On its own—and especially when taken in isolation—it can deplete the very cofactors your body needs to process it/that work alongside it, setting the stage for fatigue, nutrient imbalance, and even worsening nausea over time.
The 100 mg I cited above is over 50 times the recommended daily allowance (RDA) of B6 set by the USA. That isn’t intrinsically meaningful, of course, but it should make you pause when you consider that countries like Australia require a toxicity warning on any supplement exceeding 10 mg B6 per dosage.
Meanwhile Japan limits B6 intake during pregnancy to 45 mg per day, and Europe sets the upper limit at 12 mg per day.
The reason for such limits lies in a vague idea that B6 causes “toxicity.”
B6 is not really itself “toxic,” per se. Rather, it’s potential harms are more likely yielded by what I’d call metabolic derangement—or metabolic disequilibrium.
B6 Is Not Really “Toxic.” Rather, it’s very biochemically powerful, so to speak.
What vitamin B6 does to the body is not necessarily jam itself into aberrant locations and yield a picture of toxicity. Rather, it appears to be exerting its harms by “overdriving” appropriate metabolic pathways.
In other words, it’s going where it’s supposed to go, and it’s hyperactivating those pathways to a degree that you do not want, thus yielding a state of metabolic disequilibrium.
Of course, this is part of how B6 actually helps the nausea and vomiting of pregnancy: It goes to the chemoreceptor trigger zones in the central nervous system and (it is thought, though the science isn’t certain yet) it “hyperactivates” specific enzymes that ultimately quells overactivity of the nervous system at those spots, potentially through GABA, serotonin, and other neural signaling molecules, producing less of a neurological impulse to feel nauseous or to vomit.
But that very same hyperactivation has the potential to yield metabolic derangement as well, alongside the symptomatic improvements in nausea and vomiting.
How B6’s Metabolic Hyperactivation Has the Potential to Cause Biochemical Derangement
Vitamin B6 is an extremely robust molecule with an impact of hundreds—if not thousands—of different metabolic pathways in the human body. It has the potential to impact:
Neurotransmitter synthesis, including serotonin, dopamine, GABA, norepinephrine, and histamine
Amino acid metabolism, particularly transamination, deamination, and decarboxylation reactions
Sulfur amino acid pathways, including methionine, homocysteine, and cysteine interconversion
Glutathione synthesis, via regulation of cysteine availability and transsulfuration
Heme synthesis, through its role in δ-aminolevulinic acid (ALA) production
Glycogen breakdown, as a cofactor for glycogen phosphorylase in muscle and liver
Niacin (B3) synthesis from tryptophan, via kynurenine pathway enzymes
Hormone sensitivity modulation, including estrogen, cortisol, and androgens via steroid receptor coactivation
Immune cell function, especially lymphocyte proliferation and interleukin synthesis
Histamine clearance, through activation of histidine decarboxylase and downstream catabolism
Lipid metabolism, indirectly via carnitine biosynthesis and acetyl-CoA dependent pathways
Methylation balance, through interaction with folate, B12, and SAMe cycles
Nucleic acid metabolism, particularly via influence on 1-carbon transfer reactions
Cognitive and neurodevelopmental processes, due to its regulatory role in GABA and dopamine tone
Mitochondrial energy production, through indirect effects on CoA-dependent acetylation and redox cycling
and so on…
That’s a boon as well as a problem.
It’s a boon if you’re correcting a deficiency, or subtly compensating for a genetic deficit in one or more of these pathways that can be overridden by additional B6 supplementation.
Excess Vitamin B6 Has the Strong Potential to Bottleneck Other Essential Nutrients and Cofactors
But—very importantly—it’s a problem if you give so much B6 that these metabolic pathways (all several hundreds to thousands of them) end up being pushed to function so quickly that they lead to the bottlenecking of other important nutrients and cofactors.
This is a well-supported clinical pattern.
For example, when B6 drives the conversion of homocysteine to cysteine through the transsulfuration pathway, the increased metabolic flow creates higher demand for magnesium, zinc, and riboflavin (B2) to support the associated enzymatic steps. If those nutrients aren’t available in parallel, the pathway stalls, intermediates accumulate, and downstream processes like glutathione synthesis or sulfur clearance can become impaired.
More broadly, B6 plays a central role in amino acid metabolism—not just transsulfuration, but nearly every transamination and decarboxylation step across the urea cycle, neurotransmitter pathways, and nitrogen balance.
When B6 is present in high concentrations, these reactions accelerate, but they do so by consuming additional cofactors—niacin (B3) to support NAD⁺-dependent dehydrogenases, iron for aromatic amino acid decarboxylase and heme synthesis, and most critically in this context, pantothenic acid (B5) to sustain Coenzyme A availability for continued downstream processing.
The Critical Effect of Vitamin B6 on Pantothenic Acid
Pantothenic acid is an absolutely essential nutrient.
It is the direct precursor to Coenzyme A (CoA), a molecule required at virtually every major metabolic intersection. Without adequate B5, CoA synthesis is impaired, limiting energy production, detoxification, and hormone synthesis.
CoA is essential for:
Fatty acid oxidation, in that it transports long-chain fatty acids into mitochondria for ATP production
Krebs cycle entry, in that it converts pyruvate to acetyl-CoA and initiates cellular respiration
Steroid hormone biosynthesis, as it is required for adrenal hormones: cortisol, aldosterone, progesterone, etc.
Acetylcholine synthesis, in that it combines with choline to form this key neurotransmitter
Amino acid catabolism, in that it conjugates with organic acids to detoxify nitrogen-containing intermediates
Phase II detoxification, because it is involved in acylation and bile acid conjugation pathways
When B6 supplementation increases amino acid flux (e.g. via transamination and decarboxylation) CoA demand rises accordingly. If pantothenic acid isn’t repleted in parallel, the result is a functional CoA bottleneck, which may clinically present as:
Fatigue that intensifies with physical exertion or mental concentration
Delayed or poor recovery from stress; low AM cortisol output
Irritability or sluggishness after high-protein meals
Hormonal fluctuations or intolerance to fasting
Blunted affect, low motivation, or cognitive fog—even with sufficient B6 and methylation support
Those experiencing such symptomatic changes while on vitamin B6 would do well to consider bottlenecking of B5 (or other nutrients).
Why Pantothenic Acid Deficiency Matters in Pregnancy
Many pregnant women consume quantities of B5 well below the 6 mg that’s considered adequate for pregnancy. This is relevant, because it is currently believed that pregnancy actually significantly increases demands on vitamin B5 to fuel the creation of CoA for the baby’s developing brain.
Pregnant women, on average, have lower B5 levels in their blood than non-pregnant women, likely reflecting this increased demand.
One U.S. study found 36% lower blood pantothenic acid in pregnant women and teens compared to non-pregnant women.
Yet another study found that pregnant teenagers had ~45% lower total blood B₅ vs controls, even with around 7 mg/day of combined dietary and supplement intake in most of them.
This is extremely meaningful. B5 deficiency in pregnancy has the potential to lead to problems in both mother and child, including:
Maternal fatigue and reduced metabolic resilience, due to impaired CoA-dependent energy production
Adrenal dysfunction or blunted cortisol response, as CoA is essential for steroid hormone biosynthesis
Poor stress recovery and increased emotional lability, linked to reduced synthesis of acetyl-CoA–derived neurotransmitters
Neuromuscular symptoms such as burning feet, paresthesia, and muscle cramps (seen in early-stage B5 insufficiency)
Impaired fetal development, particularly of the brain and adrenal glands, which depend on CoA for lipid and hormone synthesis
Low birth weight or delayed growth, observed in animal models with restricted pantothenic acid availability
Potential increased risk of congenital abnormalities, though human data are limited and require further investigation
Compromised postnatal milk quality, as pantothenic acid is required for mammary gland energy metabolism and secretion
In short: B5 status is already a problem in pregnant mothers. Excessive B6 intake—which is exceedingly common in pregnant women—has the potential to worsen this deficit even further and potentially lead to fatigue, neurological, hormonal, and other problems in both mother and child.
The solution to this, of course, is twofold:
Firstly: B6 supplementation during pregnancy has to be both highly personalized and monitored through blood testing.
Sufficiency should be assessed not just by serum B6 levels, but also in context with symptoms, nutrient interactions, and metabolic demands. In cases where higher-dose B6 is actually needed, regular monitoring helps prevent oversaturation, cofactor depletion, and downstream metabolic derangement and disequilibrium.
Secondly: B6 should almost never be given in isolation. It must be accompanied by a carefully balanced selection of nutrients and cofactors—tailored to the individual—but often including, in particular, pantothenic acid (B5), riboflavin (B2), niacin (B3), and thiamine (B1), in moderate, titrated, and monitored dosages, with the goal of supporting the full range of enzymatic reactions that B6 affects.
In pregnant women under high stress or elevated amino acid flux, it is empathically not optional to ensure targeted repletion.
