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Nutritional Supplements that Can be Counterproductive

Although many nutritional supplements can be beneficial and support health, that is not always the case. In some circumstances, particular supplements can be highly counterproductive or even harmful. It is vital to be informed about potential complications to optimize your results and prevent a setback in your healing journey.

This discussion is an expansion from a previous web post on what do when nutritional supplements make you worse. Please refer back to that article for more in-depth information about the whys and whats of intolerance to nutritional supplements. In this discourse, we will be focusing primarily only on some of the specific nutrients that have the capacity to be problematic and who is likely to have a negative experience.

However, to review from our former discussion, nutritional supplements can be counterproductive in the following primary ways.

Increases Glutamate

Glutamate is an important excitatory neurotransmitter. However, in excess, it is an excitotoxin and can lead to a wide array of neurological and gastrointestinal symptoms like autism, migraines, anxiety disorders, restless legs, insomnia, OCD, seizures, abdominal pain, acid reflux, proliferation of pathogenic microbes, increased risk of stroke and much more, as discussed on the following page.

Elevates Histamine

Histamine is also a vital excitatory neurotransmitter, but in excess it is toxic and contributes to many physiological and psychiatric symptoms, like migraines, insomnia, OCD, anxiety, flushing, sex or gambling addiction, high levels of fear, hives, gastrointestinal distress, excess sympathetic nervous system activity and more, which you can learn more about here.

Increases Norepinephrine & Triggers Stress Response System

Norepinephrine is another excitatory neurotransmitter that is toxic to the brain when in excess, leading to symptoms like insomnia, anxiety and fear, restlessness, impaired digestion, weakened immunity, and elevated blood sugar, to name a few. It sets off the stress response system. If it remains in excess, one remains in sympathetic stress continuously. Learn more about this on this page.

This issue tends to be more problematic for people who are under-methylators. Methylation is needed to get rid of norepinephrine.

Increases Acetylcholine

Another critical neurotransmitter that regulates the autonomic nervous system and is vital for proper brain function, but when it is in excess, it overstimulates the sympathetic nervous system and results in symptoms like anxiety, fear, insomnia, depression and more.

Spikes Cortisol

Cortisol is a hormone that is vital for life, but when in excess it can lead to weak immunity, impaired brain function, panic attacks or high levels of anxiety and fear, lower bone density, muscle loss, and sleep problems.

If cortisol stays spiked too long and too often, it can lead to depletion, which can result in loss of energy and stamina, chronic fatigue, inability to cope, blood sugar dysregulation, chronic pain, inflammation, allergies, and autoimmune disorders.

Feeds Microbes

Like humans, microbes have nutritional needs. When they inhabit the human body, they steal our nutrients for their survival. Supplementation of nutrients they require can provide them with the food they need to proliferate.

Increases Estrogen

Estrogen is another essential hormone, but when in excess it leads to estrogen dominance and symptoms like anxiety, irritability, rage, headaches or migraines, ovarian cysts, blood sugar problems, muscle cramps and more.

Genetic Mutations

There’s a wide variety of genetic mutations that can affect how one will respond to a particular nutrient in a supplement. A nutrient that helps one condition can exacerbate another condition. It may be necessary to address issues in a particular order. This issue is beyond the scope of this article so we will not be covering it in detail. I suggest you take a look at Autism: Pathways for Recovery, by Dr. Amy Yasko for more in-depth information on this topic.

Most Common Nutrients that can be Problematic

Please note this list is not complete. These are some of the most common supplements to cause a problem and I will likely update the list periodically when more come to light. If you know of some that are not on the list, you can send them to me in the comments section below and I’ll add it to the post.

Glutamine, Glutamic Acid, GABA, Cysteine, Aspartate, Aspartic acid, Glutathione

All of these can increase glutamate.

Furthermore, some bacteria in the gut convert glutamine into glutamate. If one has an excess of these types of bacteria, which could be the case in SIBO, then glutamine may contribute to excess glutamate. Additionally, some gut bacteria eat glutamine, so in people who have SIBO, glutamine can cause proliferation of SIBO, and toxins from SIBO can lead to excess glutamate.

People who are vulnerable to anxiety, sympathetic dominance or dysautonomia, advanced adrenal fatigue, MCS, autism, insomnia, OCD, addiction, SIBO, or any condition associated with excess glutamate, should watch out for all these substances.

Glutamine can also be harmful to be people with liver disease, as the liver may incapable of utilizing it properly.

Citrate or Citric Acid

Most citrate or citric acid is derived from corn, which can result in trace amounts of glutamate or aspartate during processing. As described above, both of these can increase glutamate.

Amino Acid Formulas or Protein Powders

Can increase glutamate and norepinephrine.

Undermethylators, people prone to anxiety, sympathetic dominance or dysautonomia, advanced adrenal fatigue, autism, insomnia, OCD, addiction, multiple chemical sensitivities, or any condition associated with excess glutamate or excess sympathetic nervous system activity, should be aware of this potential.

Whey Powder

Increases glutamate.

It is also a very concentrated form of casomorphins. Casomorphins are morphine-like substances that occur naturally in whey and casein. Some people have problems breaking down casomorphins and they can lead to a host of psychological disturbances like OCD, depression, eating disorders, autism, schizophrenia, psychoses, and addiction. People with any of these conditions should consider the impact of whey. You can read more about casomorphins here.

Again, anyone with addiction issues, anxiety disorders, autism, insomnia, sympathetic dominance or dysautonomia, advanced adrenal fatigue, MCS, OCD, or any condition associated with excess glutamate or casomorphins, should exercise caution with whey.

Collagen and Gelatin

Both of this can increase histamine and glutamate. May possibly feed SIBO.

They can be problematic for anyone with excess glutamate or histamine and the many associated conditions already discussed like sympathetic dominance, anxiety disorders, insomnia, OCD, adrenal fatigue, and more. People with SIBO should exercise caution and monitor their response.


May increase cortisol.

People with adrenal fatigue, high cortisol, prone to anxiety, under-methylators, insomnia, or any condition associated with excess sympathetic nervous system activity should be aware of this potential


Tryptophan can go down one pathway and create serotonin. However, it can go down another pathway and become quinolinic acid. If one is experiencing high levels of inflammation (immune stimulation), stress, or infection, it can drive tryptophan to be converted mostly into quinolinate instead of serotonin. High levels of quinolinic acid are neurotoxic, which can cause a myriad of problems in the brain and nervous system.

Tyrosine or Phenylalanine

Both can increase norepinephrine.

Phenylalanine is converted into tyrosine.

Tyrosine is converted into dopamine and dopamine is converted into norepinephrine and then norepinephrine is converted into epinephrine and burnt off. If you do not convert your norepinephrine into epinephrine quick enough, then norepinephrine can become elevated.

This supplement is usually an issue for people who are under-methylators. Methylation is required to convert the norepinephrine into epinephrine. So under-methylators as well as people with conditions like anxiety, insomnia, restlessness, adrenal fatigue, sympathetic dominance, should be careful with these nutrients.

Tyrosine and phenylalanine can increase your blood pressure. Anyone with a history of melanoma should not take tyrosine or phenylalanine. Tyrosine and phenylalanine can also have a negative impact on hyperthyroidism, Hashimoto’s, and the manic-depressive.


Some types of probiotics can increase histamine and d-lactate. Both histamine and D-lactate are neurotoxic when in excess.

If SIBO is present, and the overgrowth involves friendly bacteria, then probiotics can exacerbate this condition.

People with high histamine, SIBO, or elevation in D-lactate should exercise caution with probiotics.

Furthermore, in severe dysbiosis, organisms present in a probiotic can become pathogenic. This includes the soil based organisms as well.


Can increase glutamate. Particularly when taken without magnesium, or in a high dose.

Glycine or Glycinate

In people who tend to lean towards excess glutamate, it can increase glutamate.

Taurine (Taurate) or GABA

Increases GABA, but because of the GABA shunt, GABA is turned back into glutamine, which gets converted into glutamate.

People who have problems converting their glutamate to GABA may have a problem here with an elevation of glutamate.

Can also cause complications for people who have CBS or SUOX genetic mutations.


This is a glutamate analog. If you have problems converting your glutamate to GABA, it can result in excess glutamate.

May also contain trace amounts of fungi or caffeine.

Plant Based Digestive Enzymes

Most are derived from fungi.

These can be problematic for people with Candida or mold issues.

Resistant Starch

Is a major food source for bacteria. Can cause a significant deterioration in health for people with SIBO or bacterial overgrowth in the colon.

Anyone with SIBO or conditions related to SIBO like IBS, GERD, acid reflux, heartburn, or other types of bacterial overgrowth should avoid this supplement. Learn more about resistant starch to understand this issue completely.

Flax Seeds

Very high in phytoestrogens, which increases estrogen levels.

Anyone who is estrogen dominant should be cautious. People with Candida are often estrogen dominant, so they should be aware as well.

Fish Oil

Is a high histamine substance. Anyone with high histamine should be aware of this issue.

Can be contaminated with heavy metals.


Candida uses magnesium for survival, morphogenesis, and construction of the biofilm. All other microbes use magnesium for biofilm construction as well. Oral magnesium supplementation may contribute to overgrowth.

People with Candida or some other type of microbial overgrowth should be aware of this potential issue.

Other Minerals

In addition to magnesium, many microbes use calcium, zinc, and iron for survival and biofilm development. Supplementation can contribute to overgrowth.

Minerals and all supplements can be problematic for people with kidney disease.


All species of Candida need biotin for survival. Therefore, supplementation can cause proliferation in overgrowth.

Other B Vitamins

Candida glabrata and a variety of other Candida species use B6 for their survival. Some species and strains of Candida use thiamine and B3 for survival. Many microbes use B12 for survival. Therefore, these B vitamins can cause proliferation of Candida. Some B vitamins can be problematic for people with certain genetic mutations and they can be too stimulating for some people for various reasons like boosting energy production too quickly or triggering sympathetic nervous system response.

Niacin (B3) also releases histamine, so can be very problematic for the individual with high histamine.

Some Vegetarian Capsules

Some vegetarian capsules contain an ingredient that triggers glutamate. I am not sure what the substance is, as it isn’t listed, but I’m sure of its impact on glutamate.

Supplements that Incite Die Off or Mobilize Toxins

Anything that is taken to kill a microbe or mobilize toxins has the potential to increase norepinephrine, glutamate or histamine, because of toxicity and die off and may set off the stress response system.

Adrenal Glandulars

Increases norepinephrine and cortisol. Even people who aren’t producing enough cortisol can have problems here, particularly when they have advanced stage adrenal fatigue because it is too stimulating and will cause more deterioration.


For reasons not understood, some people can have the complete opposite effect than what is expected with this supplement, including depression, anxiety, paranoia, and fear.

Choline or Lecithin

Increases acetylcholine, thus it can increase sympathetic nervous system activity. It can also have a negative effect on Parkinson’s.


Feeds bacteria and Candida.


Feeds SIBO.

Inositol or Glycerol

Both of these are polyols that feed SIBO.


Can feed some species of Candida and bacteria. It is also too stimulating for most people with advanced stage adrenal fatigue.

Vitamin D

Vitamin D increases calcium levels. As mentioned previously, if calcium is elevated relative to magnesium, it can increase glutamate.


Is an MOA (monoamine) inhibitor and, therefore, can increase norepinephrine, dopamine, and serotonin. It also decreases histamine, which could be problematic for someone who has low histamine.


Any supplement that contains an ingredient you have a sensitivity or allergy towards has the potential to increase norepinephrine because this will set off the stress response system.

Many different supplements may interact with antidepressants.

If you are on dialysis, have kidney disease, liver disease, high blood pressure, a history of melanoma, mania, or any other mental or physical health condition, suffer from Parkinson’s, or taking an antidepressant, then it is critical that you consult with your physician before using any nutritional supplements.

Herbs that can be Counterproductive

Most herbs have some impact on neurotransmitters in the brain. Additionally, they can affect other organs and systems and be accompanied by a wide variety of other side-effects. Therefore, there is always the potential for a negative reaction with an herb and I will not go into this category in detail in this discussion.

Furthermore, it’s important to distinguish the difference between herbal formulas and nutritional supplements. Herbs are not nutrients and they are not assimilated by the body in the same way. Herbs are natural drugs and seen by the body as such. Just because something is natural does not mean it is safe or free of side-effects. Supplementing with herbs should be done in the same manner as a pharmaceutical, with caution and being aware of potential problems prior to consumption.

Any herb that is used as an anti-depressant or anti-anxiety medication will ultimately lead to more depletion an imbalance in neurotransmitters. The brain responds to herbs in the same manner as it responds to pharmaceutical based substances that target neurotransmitters, with downregulation in production or reduced responsiveness of said neurotransmitter.

Although you should be cautious with all herbs, I do want to highlight a few of the most important that can produce the results we are discussing today.

St. John’s Wort – increases norepinephrine.

Olive Leaf – is an MOA inhibitor that can increase serotonin, dopamine, norepinephrine, and phenylethylamine (another excitatory neurotransmitter).

Neem – lowers blood sugar very significantly, which would also set off the stress response system.

Cinnamon – increases histamine.

Ginseng – is an amphetamine that will elevate norepinephrine.

Licorice – increases cortisol and norepinephrine. This can be counterproductive even for some people who are not producing adequate levels of cortisol (usually advanced stage adrenal fatigue), because it is too stimulating, which weakens the adrenals even further. The same is true for adaptogenic herbs in people with advanced stage adrenal fatigue.

Berberine – inhibits the enzyme known as acetylcholinesterase which is needed to break down acetylcholine, which allows acetylcholine to become in excess.

Assess and Adjust Accordingly

It’s also important to be aware that just because a particular nutrient is on this list, doesn’t mean it will be counterproductive for everyone. Some people can take these nutrients without any problem and they can be beneficial. If you don’t have any of the problems typically associated with the complication, then they may be perfectly acceptable. The people who tend to have the most issues with these supplements are usually those who are prone to experience dysautonomia (otherwise known as sympathetic dominance or excess sympathetic nervous system activity), anxiety disorders, advanced stage adrenal fatigue, insomnia, and under-methylators. Assess how you respond to each nutrient and adjust accordingly.

Additionally, in some cases, it may be necessary to weigh the benefit against the adverse effect. If there is a nutritional need that is greater than the risk of use, a person may choose to put up with a side-effect in order to reap a particular benefit.

8 thoughts on “Nutritional Supplements that Can be Counterproductive”

  1. Thank you very much for this extremely helpful article Cynthia. I have had some of these reactions and have had some of the flipside experiences you speak of here but I have never seen such a well-written article.

  2. Phenomenal article, phenomenal website. Thank you so much for the time you spent getting this all down for others to read.

  3. Hello, can you please tell me if Vitamin C can ever cause adverse reactions in people who are trying to balance neurotransmitters? I didn’t see it listed in this article but thought I’d ask anyway. My husband has been experiencing psychosis after years of abusing his Adderall rx (which he recently went off of cold turkey) and also going off of Seroquel cold turkey, which was prescribed to help him sleep. I’m working on trying to help him balance his neurotransmitters and he’s had adverse reactions to several different supplements I’ve given him, including B12/Folate, Lithium Orotate, and Phosphytlserine. In addition to those, he’s had bad reactions to St. John’s Wort, Valerian Root, and over the counter sleep aids. I know Vitamin C is an essential co-factor to many different neurotransmitters and bodily processes, but I’m nervous about having him try it since he’s had bad reactions to those other supplements, all of which caused him to get overly excited, extremely aggressive, and worsened his symptoms of psychosis. Any insight you could give me would be very much appreciated. Thanks so much!

    1. Admin - Cynthia Perkins

      Hi Jen,

      There is potential for adverse reactions with any supplement when dealing with a complex situation. Whether your husband will have a problem I can’t say.

      However, generally speaking, vitamin C is not too problematic for balancing neurotransmitters. High dose vitamin C is very effective for assisting with drug detoxification. When used in combination with a high protein diet, very high dose vitamin C has been shown to be very effective for alleviating withdrawal symptoms from heroin addiction. And in higher doses is more effective than methadone at eliminating cravings. In clinics using nutritional support for drug detox, vitamin C is at the top of the list regardless of the drug of choice.

      You should also take a look at the following page to learn more about balancing neurotransmitters.


      And pick up a copy of the book End Your Addiction Now by Dr. Charles Gant.



  4. Thank you for another great article and helping guide me along my healing journey. I’m learning so much from you! I have high cortisol levels and sympathetic dominance and now realize that the Adrenal Glandular supplement I’m taking is working against me, so I’ll be weaning myself off of it right away. I also take another adrenal support supplement with the main ingredients Rhodiola and Relora. Is it possible that this could also be contributing to my excessively high cortisol levels and hindering my ability to heal?

    1. Admin - Cynthia Perkins

      Hi Kirk,

      You’re welcome. I am not in favor of those herbs for the adrenal glands. Yes, they can be problematic as well.

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