Alzheimer’s Disease and Nitric Oxide
September 21st is World Alzheimer’s Day, an internationally recognized day to increase awareness of dementia-related diseases with walks and other fundraisers and educational events. Nitric oxide dysregulation may play a part in the onset of dementia, learn more about it here.
What is Alzheimer’s Disease?
The federal National Institute of Aging defines Alzheimer’s disease as:
“an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and, eventually, the ability to carry out the simplest tasks”.
If you have had family or friends who reached their senior years, you have probably been affected by the toll that this disease can take on a person and the people who take care of them. Watching somebody’s mental health unravel in slow motion is truly tragic. We think that it’s important for everyone to have access to the facts, so keep reading if you’d like to know more.
Only about 1% of the U.S. population has clinically diagnosed Alzheimer’s disease, however this number doesn’t tell the whole story. Dementia-related diseases may take decades to progress to a diagnosable stage. The most accurate study estimates that 47 million Americans have preclinical Alzheimer’s disease, meaning that 1 in 7 people alive today will most likely experience the cognitive decline - “dementia” - of Alzheimer’s in their life.
Alzheimer’s disease is essentially a “vascular” disease - meaning when you strip away the differences between all the different theories of how it happens, the common denominator is that the blood flow and nutrients available to the brain are impaired.
Like many other chronic conditions, it is associated with increased oxidative stress, which can be fought off with antioxidants like vitamins or plants chemicals like anthocyanins in blueberries or curcumin in turmeric.
Like many other heart diseases, Alzheimer’s is linked to decreased nitric oxide - “NO”, a strong signalling molecule that can be enhanced by supplementing with natural nitrates. Aging also leads to lower NO, but it appears that the decrease in all three types of NO synthase in all stages of Alzheimer’s is independent of age.
Preventing Alzheimer’s is a complicated topic. There are ways to reduce your risk, but there is no silver bullet when it comes to this kind of brain disease. Some experts think of adopting healthy lifestyle changes more as a way to slow down the progression in people who might otherwise have been hospitalized or died from the disease earlier. So, if you could make choices now that may give you extra years to thrive, would you?
How do you lower the risk of getting Alzheimer’s Disease?
There are 4 pillars for reducing your risk of Alzheimer’s disease according to the Alzheimer’s Research & Prevention Foundation:
- Healthy diet and supplements
- Exercise, physical and mental
- Stress management
- Psychological well-being & sociability
Aerobic physical exercise is the only pillar of Alzheimer’s prevention with very high level evidence, sop make sure you get at least 150-190 minutes of exercise that raises your heart rate every week. That’s 20-30 minutes of breathing hard every day.
The most commonly recommended next step is focusing in on a Mediterranean diet - a way of eating that limits processed foods and encourages lots of olive oil, fish, and plenty of vegetables. There is also promising, but not definitive, research in support of eating more wild blueberries and supplementing with fish oil for some people.
There are many supplements out there that claim to prevent Alzheimer’s disease, but don’t fall for the hype. The FDA has listed many companies as falsely advertising their products, and The Global Council on Brain Health has issued a statement that no supplements have been proven for Alzheimer’s prevention.
But there are limitations to the funding, design, and interpretation of many scientific studies - we know that personalized supplementing can be considered on an individual basis with the guidance of a licensed healthcare provider.
For example, low B12 and low folate levels are directly linked to Alzheimer’s symptoms, so getting foods that are high in those throughout life is very important, and a supplement may be necessary for people with poor methylation status (more on methylation at this blog post).
Other supplementation protocols may include the anti-inflammatory curcumin, the antioxidant Vitamin E, the memory-enhancer gingko biloba, or the ketogenic MCT oil. The Alzheimer’s Association reviews these and other supplements cautiously yet hopefully, knowing that they may have some benefit for some people. The U.S. federal government’s National Center for Complementary and Integrative Medicine, however, has the strictest standards and does not recommend any supplements for Alzheimer’s treatment or prevention. For another opinion, check out the Alzheimer’s Drug Discovery Foundation’s Cognitive Vitality Ratings
Dementia and Nitric Oxide
The role of heart and blood health in the development of Alzheimer’s is very clear to researchers. Some go so far as to point the finger to insulin spikes and sugar imbalance, referring to Alzheimer’s as “Type III diabetes”. Other researchers show that a common link between heart disease and memory loss is the nitric oxide signalling pathway. Studies in mice confirm this, and research in humans shows that the theory at least makes sense - enough so that others are even testing out different nitrate molecules as treatments.
Unfortunately there has been no high quality clinical research to show whether boosting nitric oxide can help with Alzheimer’s. There is one small, low-quality study that showed a positive effect on cognitive impairment with L-arginine, a supplement that can raise nitric oxide levels. We know from other studies that natural nitrates from beets raise nitric oxide levels substantially more than arginine. The blend of beets, red spinach, and aronia berry used in Resync’s blends packs an even greater punch.
As we pointed out earlier though, even if only 3.5 million adults have clinically recognized Alzheimer’s, the disease begins much earlier in life and progresses silently. And fortunately for us, there is a significant amount of research that shows the dietary nitrates found in Resync Collagen and Resync Recovery can help older people’s exercise and might aid memory. As a clinically studied exercise and heart health aid, it seems that the nitric oxide theory of cognitive decline may have some weight.
Some takeaways from reviewing the science:
- Eating nitrates (like in spinach or beets), might not be enough for older people to get the benefits - they may benefit from a more concentrated supplement.
- Older adults may need to supplement with beet juice for longer than one week to get the exercise benefits, or they may need a stronger supplement than beet juice.
- Even though a standard dose of natural nitrates didn’t appear to show up in the brain, only when scientists looked at specific brain regions did they see the benefits of beets.
- However, some of these studies, and particularly this very-well done study, have shown that the exercise benefits of beets do not always extend to the mental benefits
- But other studies do show cognitive enhancement.
- In a very high-quality study, nitrate supplements do lower inflammation and boost the brain’s immune system.
As you can see, understanding this research can be challenging, even for doctors and scientists. The mixed results of these studies goes to show that there really is no one-size-fits all approach.
When thinking about a disease that affects us where we’re the most individualized - in our brains - it’s important to find the helpful support of a medical specialist in this field to help you and your loved ones navigate toward a brighter and clearer future. Please look through the following resources for more information!
For some not so light reading, check out these scientific reviews:
And if you want to learn even more about this fascinating topic, see this list of related articles on pubmed.
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Acute Effect of a High Nitrate Diet on Brain Perfusion in Older Adults. - PubMed - NCBI. https://www.ncbi.nlm.nih.gov/pubmed/20951824. Accessed 20 Sept. 2019.
“Alzheimer’s Disease Fact Sheet.” National Institute on Aging, https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet. Accessed 20 Sept. 2019.
Brookmeyer, Ron, and Nada Abdalla. “Estimation of Lifetime Risks of Alzheimer’s Disease Dementia Using Biomarkers for Preclinical Disease.” Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, vol. 14, no. 8, Aug. 2018, pp. 981–88. www.alzheimersanddementia.com, doi:10.1016/j.jalz.2018.03.005.
Cifuentes Diana, et al. “Inactivation of Nitric Oxide Synthesis Exacerbates the Development of Alzheimer Disease Pathology in APPPS1 Mice (Amyloid Precursor Protein/Presenilin-1).” Hypertension, vol. 70, no. 3, Sept. 2017, pp. 613–23. ahajournals.org (Atypon), doi:10.1161/HYPERTENSIONAHA.117.09742.
Dietary Nitrate Does Not Affect Physical Activity or Outcomes in Healthy Older Adults in a Randomized, Cross-over Trial. - PubMed - NCBI. https://www.ncbi.nlm.nih.gov/pubmed/27890482. Accessed 20 Sept. 2019.
Effects of Short-Term Dietary Nitrate Supplementation on Blood Pressure, O2 Uptake Kinetics, and Muscle and Cognitive Function in Older Adults | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. https://www.physiology.org/doi/full/10.1152/ajpregu.00406.2012. Accessed 20 Sept. 2019.
Effects of Short-Term Dietary Nitrate Supplementation on Blood Pressure, O2 Uptake Kinetics, and Muscle and Cognitive Function in Older Adults | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology---. https://www.physiology.org/doi/full/10.1152/ajpregu.00406.2012. Accessed 20 Sept. 2019.
Frontiers | Impact of Nitric Oxide Bioavailability on the Progressive Cerebral and Peripheral Circulatory Impairments During Aging and Alzheimer’s Disease | Physiology. https://www.frontiersin.org/articles/10.3389/fphys.2018.00169/full. Accessed 20 Sept. 2019.
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Inactivation of Nitric Oxide Synthesis Exacerbates the Development of Alzheimer Disease Pathology in APPPS1 Mice (Amyloid Precursor Protein/Presenilin-1) | Hypertension. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.117.09742. Accessed 20 Sept. 2019.
Kawamoto, Elisa Mitiko, et al. “Oxidative State in Platelets and Erythrocytes in Aging and Alzheimer’s Disease.” Neurobiology of Aging, vol. 26, no. 6, June 2005, pp. 857–64. PubMed, doi:10.1016/j.neurobiolaging.2004.08.011.
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Khalsa, Dharma Singh, and George Perry. “The Four Pillars of Alzheimer’s Prevention.” Cerebrum: The Dana Forum on Brain Science, vol. 2017, Mar. 2017. PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501038/.
McNamara, Robert K., et al. “Cognitive Response to Fish Oil, Blueberry, and Combined Supplementation in Older Adults with Subjective Cognitive Impairment.” Neurobiology of Aging, vol. 64, Apr. 2018, pp. 147–56. ScienceDirect, doi:10.1016/j.neurobiolaging.2017.12.003.
Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimer’s Disease. - PubMed - NCBI. https://www.ncbi.nlm.nih.gov/pubmed/15974915#targetText=Nitric%20oxide%20mimetic%20molecules%20as%20therapeutic%20agents%20in%20Alzheimer's%20disease.&targetText=Nitric%20oxide%20is%20multifunctional%20messenger,may%20be%20reduced%20with%20aging. Accessed 20 Sept. 2019.
Ohtsuka, Yoshinori, and Jun Nakaya. “Effect of Oral Administration of L-Arginine on Senile Dementia.” The American Journal of Medicine, vol. 108, no. 5, Apr. 2000, p. 439. www.amjmed.com, doi:10.1016/S0002-9343(99)00396-4.
Petrie, Meredith, et al. “Beet Root Juice: An Ergogenic Aid for Exercise and the Aging Brain.” The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, vol. 72, no. 9, Sept. 2017, pp. 1284–89. PubMed, doi:10.1093/gerona/glw219.
Plasma Nitrate and Nitrite Are Increased by a High-Nitrate Supplement but Not by High-Nitrate Foods in Older Adults. - PubMed - NCBI. https://www.ncbi.nlm.nih.gov/pubmed/22464802. Accessed 20 Sept. 2019.
Venturelli, Massimo, et al. “Impact of Nitric Oxide Bioavailability on the Progressive Cerebral and Peripheral Circulatory Impairments During Aging and Alzheimer’s Disease.” Frontiers in Physiology, vol. 9, 2018. Frontiers, doi:10.3389/fphys.2018.00169.
Vural, Huseyin, et al. “The Role of Arginine–Nitric Oxide Pathway in Patients with Alzheimer Disease.” Biological Trace Element Research, vol. 129, June 2009, pp. 58–64. ResearchGate, doi:10.1007/s12011-008-8291-8.
Wightman, Emma L., et al. “Dietary Nitrate Modulates Cerebral Blood Flow Parameters and Cognitive Performance in Humans: A Double-Blind, Placebo-Controlled, Crossover Investigation.” Physiology & Behavior, vol. 149, Oct. 2015, pp. 149–58. PubMed, doi:10.1016/j.physbeh.2015.05.035.