Can a Popular Antihistamine Drug Cause Brain Fog?

The latest research has shown that common anticholinergic drugs (diphenhydramine) like Benadryl® are linked to increased risk of dementia.

What is diphenhydramine?

Diphenhydramine is an antihistamine that reduces the effects of natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Diphenhydramine is used to treat sneezing, runny nose, watery eyes, hives, skin rash, itching, pain, cold and allergy symptoms.

Diphenhydramine is also used to treat motion sickness, to induce sleep, and to treat certain symptoms of Parkinson’s disease, but there is a price to pay. Most people who buy the following products never looks to see if they contain diphenhydramine.

Common brands that contain diphenhydramine:

  • Advil®
  • Bayer® Aspirin
  • Benadryl®
  • Dimetapp®
  • Ivarest®
  • Sominex®
  • Unisom®
  • Store brands (ex. Walmart’s “Equate” store brand or CVS Health store brand)

In a report published in JAMA Internal Medicine, researchers offer compelling evidence of a link between long-term use of anticholinergic medications like Benadryl and dementia.

Anticholinergic drugs block the action of acetylcholine. This substance transmits messages in the nervous system. In the brain, acetylcholine is involved in learning and memory. In the rest of the body, it stimulates muscle contractions. Anticholinergic drugs include some antihistamines, tricyclic antidepressants, medications to control overactive bladder, and drugs to relieve the symptoms of Parkinson’s disease.

What the study found

A team led by Shelley Gray, a pharmacist at the University of Washington’s School of Pharmacy, tracked nearly 3,500 men and women ages 65 and older who took part in Adult Changes in Thought (ACT), a long-term study conducted by the University of Washington and Group Health, a Seattle healthcare system. They used Group Health’s pharmacy records to determine all the drugs, both prescription and over the counter, that each participant took the 10 years before starting the study. Participants’ health was tracked for an average of seven years. During that time, 800 of the volunteers developed dementia. When the researchers examined the use of anticholinergic drugs, they found that people who used these drugs were more likely to have developed dementia as those who didn’t use them. Moreover, dementia risk increased along with the cumulative dose. Taking an anticholinergic for the equivalent of three years or more was associated with a 54% higher dementia risk than taking the same dose for three months or less.

The ACT results add to mounting evidence that anticholinergics aren’t drugs to take long-term if you want to keep a clear head and keep your head clear into old age. The body’s production of acetylcholine diminishes with age, so blocking its effects can deliver a double whammy to older people. It’s not surprising that problems with short-term memory, reasoning, and confusion lead the list of side effects of anticholinergic drugs, which also include drowsiness, dry mouth, urine retention, and constipation.

The University of Washington study is the first to include nonprescription drugs. It is also the first to eliminate the possibility that people were taking a tricyclic antidepressant to alleviate early symptoms of undiagnosed dementia; the risk associated with bladder medications was just as high.

“This study is another reminder to periodically evaluate all of the drugs you’re taking. Look at each one to determine if it’s really helping,” says Dr. Sarah Berry, a geriatrician and assistant professor of medicine at Harvard Medical School. “For instance, I’ve seen people who have been on anticholinergic medications for bladder control for years and they are completely incontinent. These drugs obviously aren’t helping.”

Many drugs have a stronger effect on older people than younger people. With age, the kidneys and liver clear drugs more slowly, so drug levels in the blood remain higher for a longer time. People also gain fat and lose muscle mass with age, both of which change the way that drugs are distributed to and broken down in body tissues. In addition, older people tend to take more prescription and over-the-counter medications, each of which has the potential to suppress or enhance the effectiveness of the others.

Despite decades of research, there is no cure for Alzheimer’s dementia. That doesn’t mean all hope is lost to avoid this devastating disease. Many lifestyle factors have been shown to play a role in reducing risk. Also, widely studied are the effects of herbs, vitamins and other nutrients and compounds that have some positive impact.

Current medications, at best, may slow the rate of dementia progression. So, shouldn’t we consider natural options that may do the same or better?

Let me share them with you…

Polyphenolic herbs and extracts

These antioxidant and anti-inflammatory extracts have been studied in rodents and found to be safe and effective. They are used in humans but have few clinical trials as of yet. These include extracts from green tea (EGCG), Ginkgo biloba + ginseng, blueberries (anthocyanins), grape seeds (resveratrol), curcumin, marine algae (fucoxanthin) cat’s claw, bilberry, and black currant. Here is further information on these:

  • Cat’s claw (Uncaria tomentosa) extract contains antioxidant polyphenols and proanthocyanidins; it is a strong antioxidant and anti-inflammatory, a potent enhancer of DNA repair in primary organ cultures of human skin and has been found to have a high binding affinity to beta-amyloid protein.
  • Bilberry and black currant extracts contain phenolic compounds that were shown to greatly reduce brain beta-amyloid protein and improve memory in Alzheimer’s mice.
  • Huperzine A (Huperzia serrata, an extract from moss): 200 microgram twice daily inhibits acetylcholine esterase.  Two double-blind clinical trials in China showed it to be safe and effective for the long-term treatment of Alzheimer’s dementia. It was found to be superior to Aricept, with longer lasting effects and fewer side effects. Reports from an estimated 100,000 people treated suggest low toxicity for this herb.  Additionally, it decreases neuronal cell death caused by toxic levels of glutamate, which makes it useful in strokes and epilepsy too.
  • Vinpocetine: 20 mg daily. It has been well-proven to have cerebral blood-flow enhancing and neuroprotective effects without adverse events. Several studies indicate it is useful to reduce memory loss and cognitive decline.

Amino acids

  • Acetyl-l-carnitine: 500-1,000 mg three times daily helps reverse the disease process of Alzheimer’s dementia. For example, memory and cognitive scores in Alzheimer’s patients given 2250-3,000 mg daily of Acetyl-l-carnitine improved 2.8 times better than placebo-treated subjects over 12 weeks in one study.
  • L-glutamine and L-tyrosine 3-5 grams daily also help prevent Alzheimer’s dementia progression.

Phosphatidylserine and Omega-3 oils

  • Phosphatidylserine (PS): 100 mg three times daily or 300 mg daily has been repeatedly shown in studies to improve memory in aging patients with memory complaints and early cognitive decline, yet there are a few that show no significant improvement by PS supplementation. In a multi-university study, subjects who took PS achieved a 30 percent improvement in cognitive function, including learning, memory, and recalling numbers, names and faces, and another study showed that PS supplementation had a 33 percent improvement in learning and remembering written information compared to the placebo control group. PS also works synergistically with vitamin B12 supplementation.
  • Phosphatidylcholine (lecithin): 1-2 Tbsp/day has been shown to improve cognitive function only in early stages of Alzheimer’s dementia, and there is a “therapeutic window dose” above which the beneficial effects of lecithin treatment are lost.
  • Omega-3 oil (Krill oil and/or flaxseed oil): 1-3 Tbsp/day. Omega 3 oils (DHA, EPA) are the building blocks of nerve tissue.


  • Vitamin B1 (thiamine): Thiamine is important for acetylcholine metabolism and release from the presynaptic neuron. Deficiency of thiamine has been shown to increase β-amyloid plaque accumulation of in many studies. Dosing of 3 to 8 grams daily of oral thiamine had a mildly beneficial effect in Alzheimer’s in a 1993 study although a later study in 1996 found similarly good effects with a daily dose of just 100 mg thiamine for 12 weeks.
  • Vitamins B6, B12 and folate help reduce homocysteine, a known risk factor for Alzheimer’s dementia.  Deficiency of Vitamin B12 can Alzheimer’s symptoms, and one-fourth of people aged 60 – 70 and approximately forty percent of those over age 80 are deficient in Vitamin B12, largely from poor absorption. Vitamin B12 works synergistically with phosphatidylserine supplementation.
  • Vitamin D3: a recent meta-analysis reveals that low vitamin D levels predict poor memory and other cognitive dysfunction and vitamin D repletion in these subjects improved brain executive functions while it showed no difference with control groups. A study reported in 2013 tells us that vitamin D restores suppressed synaptic transmission when given to Alzheimer’s rats.
  • Vitamin E (d-alpha-tocopherol with mixed tocopherols): 800 IU twice daily for up to 2 years is safe and has been reported to slow the progression of Alzheimer’s dementia, probably because it is synergistic with CoEnzyme Q10, an endogenous compound that decreases with age.

Natural compounds

  • Coenzyme Q10: 200 mg daily. This is shown to boost brain mitochondrial activity and provide a protective effect in rodent nerve tissue, especially when taken together with vitamin E. In 2011 a study in the Journal of Alzheimer’s Disease reported that coenzyme Q10 decreased amyloid-beta pathology and improved behavioral and cognitive performance in Alzheimer’s mice (transgenic mouse model).
  • Nicotinamide adenine dinucleotide (NADH): 10 mg/day, 30 minutes before breakfast. A small double-blind study found no evidence of progressive cognitive deterioration and significantly higher cognitive performance scores among Alzheimer’s dementia patients who took 10 mg daily for 6 months compared with those treated with placebo.

Best foods for Alzheimer’s dementia

The best foods are those with the highest complete protein, antioxidant activity, mineral content and that have an anti-inflammatory effect. To give you some ideas, consider these:

  • Wild salmon (omega-3 oil)
  • Cacao powder or dark chocolate (not chocolate bars with high sugar content)
  • Matcha (Gyokuru green tea powder): EGCG (Epigallocatechin Gallate) content as high as 10 times other green teas
  • Acai berries or blueberries (strongest antioxidants)
  • Coffee beans: regular coffee consumption has been shown in several studies to reduce dementia (from fresh ground beans, without artificial creams/sweeteners)
  • Grape juice, pomegranate juice (antioxidant resveratrol)
  • Apples (the antioxidant flavonoid, quercetin)
  • Leafy green vegetables such as spinach and collard greens (phytonutrients)
  • Avocados, unsalted nuts, and seeds (vitamin E, healthy oil)
  • Goji berries (a.k.a. wolfberries) have strong antioxidant properties
  • Allum foods: garlic, onions, chives, leeks, shallots, and scallions. These contain flavonoid antioxidants thought to reduce the Alzheimer’s disease process.
  • More great foods: bananas, brewer’s yeast, broccoli, brown rice, Brussels sprouts, cantaloupe, feta cheese, chicken, collard greens, eggs, flaxseed oil, legumes, oatmeal, oranges, peanut butter, peas, potatoes (not in excess), romaine lettuce, soybeans, spinach, tuna, turkey, wheat germ, and plain yogurt.

Remember to eliminate the following foods as much as possible: Alcohol; artificial food coloring; artificial sweeteners; colas, sodas, and high sugar drinks including fruit juice, corn syrup and high fructose corn syrup; frostings; hydrogenated fats; junk sugars; white bread; and nicotine.

To address allergies holistically for long-term relief, there are a number of natural approaches that can help balance immune defenses, reduce the chronic inflammation that aggravates symptoms, clear sinuses and reduce histamine reactions. These include the following:

  • Nutrients and herbs like quercetin, vitamin C, nettle and Bromelain
  • Anti-allergy foods like capers, apples, berries, greens and others
  • Homeopathic allergy preparations
  • Natural detoxification products like DN Detox
  • Dietary changes that eliminate inflammatory foods like gluten, sugar and trans fats
  • Neti pot therapy for nasal congestion and irritation
  • Best Rest and Melatonin as a sleep aid.

To find out more, call Doctor’s Nutrition at 1-800-824-0194 TODAY.


  1. Rose on 01/16/2020 at 3:11 PM

    I am in my 30ies and got MCI due anticholinergic medication intake for 4 years.
    Is there anything known to reverse this? Any help would be appreciated very much.

    • Victor on 01/17/2020 at 9:29 AM

      You may fill out one of our consultation forms online or call our office 10am until 5pm and ask to speak to one of the doctors. No charge for consultations, our number is 1-800-824-0194. Thank you for contacting Doctor’s Nutrition.

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