Amino acids are the building blocks for proteins. There are twenty of them. The body can make quite a few of them, but there are nine that have to come from the diet—these are considered essential. A “complete” protein is a food that by definition contains all nine. Histidine is one of those nine.
It performs a lot of important functions. Here are a few of them.
Histidine, Antioxidants, and Inflammation
Probably due to its inclusion in the dipeptide carnosine (including the amino acids histidine and alanine), histidine has been shown to have anti-inflammatory and antioxidant properties. Insufficient histidine will mean insufficient carnosine, which will compromise this system.
Higher dietary histidine was associated with lower levels of various inflammatory cytokines including TNF-α, IL-1β, and IL-6, lower C-reactive protein, and higher levels of antioxidant enzymes glutathione peroxidase and superoxide dismutase (SOD), according to this study.
Inflammation and oxidative stress both have their place, of course. But when they are chronic and unremitting, without resolution, they are a hallmark of most Western diseases.
Histidine, Metabolic Syndrome, and Weight Loss
One of the most common of these chronic Western diseases is Metabolic Syndrome, and everything that goes with it, including hypertension, heart disease, insulin resistance, diabetes, and obesity.
In addition to its anti-inflammatory and antioxidant properties, histamine has been shown to improve insulin sensitivity, and thus lead to weight loss.
Of course, histidine supplementation will only have this effect in those who are low in it—but this study showed that dietary histidine intake was much lower in those participants who were overweight or obese. Conversely, those with higher intake of histidine generally had lower fasting glucose.
We might conclude that this just means eating more protein (relative to carbs) leads to weight loss, which is what those following the ketogenic, paleo, and carnivore diets would likely assert — and there is some truth to this. But this study and this one show that histidine supplementation specifically improves insulin resistance, BMI, and fat mass. This study also suggests that histidine, as a precursor to histamine, will regulate feeding behavior, lowering food intake.
Histidine has also been shown to lower blood pressure too. This study suggests that it may do this by decreasing sympathetic output (less fight-or-flight) via the histamine receptor, as well as by promoting nitric oxide release. This study, meanwhile, speculates that histidine decreases blood pressure via the cardiovascular-protective L-carnosine production.
Histidine, Attention, Memory, Focus, and Mood
Histidine is the precursor to histamine, which is also a neurotransmitter associated with wakefulness, memory, and focus.
This study showed that histidine supplementation decreased fatigue, improved attention, working memory, and cognition, and balanced mood, as well. This study showed the same result.
Interestingly, low levels of histidine were associated with increased anxiety in animal studies too, further supporting its mood balancing effects.
Histidine and Histamine
Because histidine is the precursor for histamine, it’s also required for stomach acid production—low levels may be one reason why HCl could be low.
Of course histamine is traditionally thought of in conjunction with allergies, and excessive release of histamine (Mast Cell Activation Disorder) or inability to break histamine down (histamine intolerance) certainly do involve histamine. But histamine itself does quite a bit more than this. Also, supplementation with histidine should not lead to excessive levels of histamine, as the body gets to choose what it wants to make with it.
Histidine, Iron, and Ferritin
Histidine is also required for the body to build hemoglobin, the molecule in red blood cells that carries oxygen via iron. If iron levels are fine, but histidine is low, labs will show lower hemoglobin and higher serum iron, as it can’t get where it needs to go.
Histidine is also required to build ferritin — so this may be one reason why ferritin might be low, while serum iron levels are ok.
Histidine and pH
I wrote here on the importance of keeping cellular pH neutral or slightly alkaline.
Turns out, histidine plays a role here too, if it’s low: carnosine specifically helps to buffer intracellular pH. If histidine and carnosine levels are adequate, supplementation should not have an effect upon pH, but if they’re low, it could be significant.
Histidine and Heavy Metal Chelation
Histidine is also involved in detoxification of heavy metals, and it appears that carnosine is involved here too. It can also help protect tissue from damage due to heavy metals (possibly just by getting rid of them).
Histidine and the Myelin Sheath
Histidine is also a necessary building block for the myelin sheath, the fatty covering for the nerves. Because of this, it can be protective against neural degenerative disorders such as Alzheimer’s and Parkinson’s Disease. Carnosine specifically has been shown to protect against buildup of amyloid beta, the plaque associated with Alzheimer’s.
This study shows that people with Multiple Sclerosis tend to have lower levels of histidine as well as of other amino acids. This study also shows that in women with both Multiple Sclerosis and increased fatigue, histidine is significantly lower, compared to subjects who did not experience fatigue.
Histidine and Skin Protection
Histidine is a precursor of urocanic acid, which accumulates in the dermis and protects the skin against UV damage.
Histidine is also included in a protein called filaggrin, a natural skin moisturizer which helps to protect against atopic dermatitis—perhaps surprising, since atopic dermatitis is associated with allergies. This study shows that efficacy of oral histidine supplementation is comparable to the effects of topical steroids for atopic dermatitis.
Why You Might Be Low
Foods high in histidine include all animal proteins, as well as most other protein sources we generally think of (legumes, soy, dairy, nuts, seeds, whole grains, and eggs). In theory, then, if you consume enough protein, you’ll get enough histidine too, though vegetarians and vegans may be at higher risk of deficiency.
Folate deficiency can also increase histidine loss in the urine, as well.
I wasn’t able to find any studies to corroborate this, but I also speculate that since histidine (via carnosine) is involved in heavy metal chelation, those with heavy metal toxicity may potentially end up with deficiency, too. if this is the case, I’d imagine any high demand upon carnosine (acidic intracellular pH, for example) may also lead to histidine depletion.
