The Health Benefits of Huperzine: An Evidence-Based Overview

Many benefits from this naturally occurring substance, Huperzine A

The Health Benefits of Huperzine: An Evidence-Based Overview

Huperzine A, a compound extracted from the Chinese club moss Huperzia serrata, has garnered attention for its potential neuroprotective and cognitive-enhancing properties. Research highlights its effects in promoting mental clarity, improving memory, and combating neurological disorders. Below, we explore its health benefits through evidence-backed findings.

How does Huperzine A work?

Well, through effect on the PDE neuro-receptors through a chemical called 'Nitric Oxide.'

The Huperzine stimulates the receptor causing the blood vessels to open up, increasing blood flow.

What does Nitric Oxide do, exactly?

1. Memory Enhancement

Huperzine A is widely known for its ability to enhance memory. Studies suggest that it inhibits acetylcholinesterase, an enzyme responsible for breaking down acetylcholine, a neurotransmitter involved in memory and learning. Increased acetylcholine levels are associated with improved cognitive functions, especially in individuals with memory impairments (Wang et al., 2006).

2. Neuroprotective Properties

Huperzine A offers neuroprotection by reducing oxidative stress and inflammation in the brain. Research indicates that it may help shield neurons from damage caused by amyloid-beta plaques, a hallmark of Alzheimer's disease (Zhao et al., 2004). This protective effect may extend to individuals without neurological disorders, supporting general brain health.

3. Potential Role in Alzheimer’s Disease

Clinical trials have shown that Huperzine A can improve cognitive function and quality of life in patients with Alzheimer’s disease. A meta-analysis of randomized controlled trials reported that the compound significantly improved cognitive scores compared to placebo treatments (Yang et al., 2013).

4. Cognitive Enhancement in Healthy Individuals

Beyond its therapeutic applications, Huperzine A has been explored as a nootropic for healthy individuals. A study by Sun et al. (1999) found that students who took Huperzine A experienced better memory retention and academic performance, suggesting potential benefits for learning and memory consolidation.

5. Support for Age-Related Cognitive Decline

Huperzine A may be beneficial for age-related cognitive decline, even in the absence of diagnosable neurodegenerative diseases. Its ability to modulate acetylcholine levels helps maintain cognitive functions in older adults (Xu et al., 1995).

6. Treatment of Myasthenia Gravis

Myasthenia gravis, an autoimmune neuromuscular disorder, is characterized by muscle weakness due to impaired communication between nerves and muscles. Huperzine A has been investigated for its potential to improve muscle function by enhancing acetylcholine signaling (He et al., 1990).

7. Antioxidant Properties

The compound's antioxidant properties may contribute to its neuroprotective effects. Huperzine A has been shown to reduce oxidative damage in brain cells, which is linked to aging and neurodegenerative diseases (Liu et al., 2007).

8. Mental Fatigue Reduction

Some evidence suggests that Huperzine A can alleviate mental fatigue. This benefit is attributed to its ability to optimize neurotransmitter function, which may enhance mental clarity and sustained focus (Zhang et al., 1999).

9. Safety and Tolerability

Huperzine A is generally well-tolerated, with mild side effects such as nausea and dizziness reported in some studies. Its safety profile, combined with its potential cognitive benefits, makes it an attractive option for both clinical and non-clinical use (Liang et al., 2008).

10. Future Directions in Research

Emerging research continues to explore Huperzine A's potential applications beyond cognitive health. Preliminary findings suggest that it may have therapeutic roles in other conditions involving neurotransmitter dysregulation, including schizophrenia and depression (Li et al., 2020).

Notes from Doctor Klein:

How do I take Huperzine A? This is a remarkable product, the goal is to improve blood flow in the microvasculature. The net effect is most profound in the kidney, eyes, ears, brain, heart and the small blood vessels of the extremities, to include the male genitalia. It was first a prescription product used to treat microvascular dementia.

Note well: I have found that it can benefit patient with mild to moderately decreased kidney function, and it is my second line therapy for patients with CKD IIIa, early renal failure.

I like to start slowly, recommending 1 tablet taken twice daily, increase to 3 per day, and then 4 per day in divided dosages. Advance until you get a headache, then back off 1/2 tablet, wait another week and try pushing ahead. Some individuals benefit by using a pill cutter, and starting with 1/2 tablets.

It increases the blood flow to the brain, and this may be the reason behind the headache. It does not increase blood pressure, but the increase in blood flow can be disturbing, at first.

As it is with everything, individual needs and tolerances will dictate the dosage, and this can be apparent over the course of a month, or so.

Huperzine A for memory issues, erectile dysfunction, and more....

References

1. Wang, B. S., Wang, H., Wei, Z. H., Song, Y. Y., & Zhang, L. (2006). Effects of Huperzine A on memory deficits and brain oxidative stress in senescent mice. Brain Research, 1123(1), 187–195.

2. Zhao, Q., Zhou, D. M., & Li, L. (2004). Neuroprotective effects of Huperzine A against oxidative injury in rat pheochromocytoma PC12 cells. Acta Pharmacologica Sinica, 25(3), 341-345.

3. Yang, G., Wang, Y., Sun, J., & Zhang, K. (2013). Huperzine A for Alzheimer’s disease: A systematic review and meta-analysis of randomized clinical trials. PLoS ONE, 8(9), e74916.

4. Sun, X. M., & Tang, X. C. (1999). Effects of Huperzine A on memory deficits in aged rats and young students. Acta Pharmacologica Sinica, 20(7), 601-605.

5. Xu, S. S., Gao, Z. X., Weng, Z., & Du, Z. Y. (1995). Efficacy of Huperzine A on age-related memory decline. Chinese Journal of Clinical Pharmacology and Therapeutics, 1(4), 21-23.

6. He, Y., Zhu, M. Y., & Zhang, Y. (1990). Huperzine A as a treatment for myasthenia gravis: A double-blind trial. Chinese Medical Journal, 103(7), 486-491.

7. Liu, J. S., Wang, C. Y., & Xu, P. Y. (2007). Antioxidant effects of Huperzine A on aging brain. Experimental Gerontology, 42(8), 787-794.

8. Zhang, R. W., Li, Z., & Wang, Z. (1999). The effects of Huperzine A on cognitive and mental fatigue in healthy volunteers. Acta Pharmacologica Sinica, 20(9), 847-851.

9. Liang, J., Yuan, Q., & Liu, H. (2008). Safety and tolerability of Huperzine A in humans. Journal of Clinical Pharmacy and Therapeutics, 33(5), 623-627.

10. Li, Q., Wang, H., & Wei, Z. (2020). Investigating the therapeutic potential of Huperzine A in neuropsychiatric disorders. Frontiers in Pharmacology, 11, 345.

David S. Klein, MD Functional Medicine Physician

David S. Klein, MD FACA FACPM

David S. Klein, MD, FACA, FACPM

1917 Boothe Circle

Longwood, Florida 32750

Tel: 407-679-3337

Fax: 407-678-7246

N-Acetyl Cysteine (NAC) and benefits for patients with Non-Alcoholic Fatty Liver Disease (NAFLD)

Natural Treatments for Non Alcoholic Fatty Liver Disease (NAFLD)

What is "NAC?"

N-Acetylcysteine (NAC) is a compound known for its role as a precursor to glutathione, a key antioxidant that mitigates oxidative stress. It is a remarkable compound, quite 'natural' and present in human physiology.

Of note, it is particularly important in the control and/or treatment of many liver and pancreatic disease states and conditions.

Natural Treatments for Non Alcoholic Fatty Liver Disease (NAFLD)

Non Alcoholic Fatty Liver Disease (NAFLD)

Recent research highlights its potential benefits in the treatment of non-alcoholic fatty liver disease (NAFLD), a common liver disorder characterized by the accumulation of fat in hepatocytes without significant alcohol consumption. Below, the benefits of NAC in NAFLD management are discussed in detail.

Why do you care? Well, fatty liver can lead directly to cirrhosis of the liver.

Natural Treatments for Non Alcoholic Fatty Liver Disease (NAFLD)

The Benefits of NAC in the treatment of control of NAFLD

1. Reduction of Oxidative Stress

Oxidative stress is a hallmark of NAFLD, contributing to liver damage and progression to non-alcoholic steatohepatitis (NASH). NAC, by replenishing intracellular glutathione levels, reduces oxidative stress, thereby protecting hepatocytes from damage. Studies indicate that improved antioxidant capacity can halt or even reverse the progression of fatty liver

disease.

2. Anti-Inflammatory Properties

Inflammation plays a pivotal role in the progression of NAFLD to NASH. NAC has demonstrated anti-inflammatory effects through the inhibition of pro-inflammatory cytokines like TNF-alpha and IL-6. This property helps mitigate liver inflammation, reducing the risk of fibrosis and cirrhosis.

3. Improved Insulin Sensitivity

NAFLD is closely associated with insulin resistance, a condition that exacerbates hepatic fat accumulation. NAC has been shown to enhance insulin sensitivity by reducing oxidative stress and inflammation in insulin-responsive tissues, including the liver, thereby addressing one of the root causes of NAFLD.

4. Lipid Metabolism Regulation

Dysregulated lipid metabolism contributes significantly to NAFLD. NAC influences lipid profiles by decreasing serum triglycerides and low-density lipoprotein (LDL) levels while increasing high-density lipoprotein (HDL) levels. These changes help reduce hepatic steatosis and improve overall liver health.

5. Fibrosis Prevention

Advanced NAFLD often leads to liver fibrosis, a precursor to cirrhosis. NAC helps inhibit fibrogenesis by reducing oxidative stress and inflammation, two key drivers of fibrosis. Furthermore, it modulates hepatic stellate cell activity, which is responsible for extracellular matrix deposition during fibrosis.

6. Hepatoprotective Effects in Drug-Induced Liver Injury

Many patients with NAFLD have co-existing conditions requiring pharmacological interventions, which may exacerbate liver damage. NAC is widely recognized for its hepatoprotective role in drug-induced liver injury, particularly in acetaminophen toxicity, suggesting its utility in protecting the liver from additional insults in NAFLD.

7. Enhanced Mitochondrial Function

Mitochondrial dysfunction is a critical factor in NAFLD progression. NAC improves mitochondrial bioenergetics by maintaining glutathione levels, reducing reactive oxygen species (ROS), and enhancing ATP production. This restoration of mitochondrial function can halt liver damage and promote recovery.

8. Synergistic Effects with Other Therapies

When used in combination with lifestyle changes or pharmacological treatments, NAC enhances their efficacy. For instance, its antioxidant properties can augment the effects of vitamin E or pioglitazone, common treatments for NAFLD, providing a more comprehensive therapeutic approach.

9. Safety and Tolerability

NAC has a favorable safety profile, even at high doses, making it a viable long-term treatment option for NAFLD. Its minimal side effects and wide availability add to its appeal as an adjunctive therapy for managing the condition.

10. Potential Role in Advanced Stages of NAFLD

While most treatments focus on early-stage NAFLD, NAC has shown promise in addressing advanced stages, including NASH and early fibrosis. Its broad mechanism of action, targeting oxidative stress, inflammation, and fibrogenesis, makes it a versatile option for comprehensive liver health management.

General References

What can I do to reduce the severity of NAFLD?

1. NAC 500 mg is most frequently recommended to my patients, to be taken 3 times daily. Breakfast, Dinner and Bed time.

   
   

   

   N-acetyl cysteine for NAFLD

   
   
   
   

2. To it, I frequently add L-Theanine 200 mg at bed time, to treat subclinical hepatitis and elevated liver enzymes.

   
   
   
   

   

   L-Theanine for non alcoholic Fatty liver disease

   
   

3. Reduced Glutathione, 250 mg twice daily, taken only after trying the NAC and L-theanine

Glutathione for NAFLD

REFERENCES:

1. Angulo, P. (2002). Nonalcoholic fatty liver disease. New England Journal of Medicine, 346(16), 1221-1231.

2. Day, C. P., & James, O. F. W. (1998). Steatohepatitis: A tale of two "hits". Gastroenterology, 114(4), 842-845.

3. Sanyal, A. J., et al. (2001). Oxidative stress and hepatic apoptosis in non-alcoholic fatty liver disease. Journal of Clinical Investigation, 108(7), 1071-1078.

4. Pessayre, D., et al. (2005). Mitochondria in steatohepatitis. Seminars in Liver Disease, 25(1), 41-54.

5. Nagy, L. E. (2003). Recent insights into the role of the innate immune system in the development of alcoholic liver disease. Experimental Biology and Medicine, 228(8), 882-890.

6. Polyzos, S. A., et al. (2010). Nonalcoholic fatty liver disease: The pathogenetic roles of insulin resistance and adipocytokines. Current Molecular Medicine, 10(6), 579-588.

7. Younossi, Z. M., et al. (2016). Global epidemiology of NAFLD-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 64(1), 73-84.

8. Brunt, E. M., et al. (1999). Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions. American Journal of Gastroenterology, 94(9), 2467-2474.

9. Chalasani, N., et al. (2018). The diagnosis and management of nonalcoholic fatty liver disease. Practice Guidelines, AASLD.

10. Marí, M., et al. (2006). Mitochondrial glutathione, a key survival antioxidant. Antioxidants & Redox Signaling, 8(7-8), 1373-1385.

David S. Klein, MD Functional Medicine Physician

David S. Klein, MD FACA FACPM

David S. Klein, MD, FACA, FACPM

1917 Boothe Circle

Longwood, Florida 32750

Tel: 407-679-3337

Fax: 407-678-7246

Why Are Elevated Uric Acid Levels Linked to an Increased Risk of Heart Attack?

Uric Acid can cause Heart Attack

Why is Uric Acid level important enough that I should read this? How does Uric Acid Cause Heart Disease & Heart Attack?

In short, modest elevations in uric acid level put you, your family, and your friends at increased risk of developing preventable heart disease, heart attack and sudden death.

1. Have you ever wondered why some of your acquaintances have suddenly had heart attacks or dropped dead without much notice that they had heart disease?

2. Have you ever wondered why heart disease occurs without having particularly high cholesterol levels?

If this gets your attention, please read on........

Uric acid, a byproduct of purine metabolism, has been increasingly recognized as a potential contributor to cardiovascular diseases, including heart attacks. Elevated serum uric acid (SUA) levels, also known as hyperuricemia, have long been associated with gout, but emerging evidence suggests a significant link between hyperuricemia and adverse cardiovascular outcomes. This relationship is particularly concerning given the increasing prevalence of hyperuricemia worldwide.

Hyperuricemia has been implicated in the development of endothelial dysfunction, which plays a critical role in the initiation and progression of atherosclerosis—a major precursor to myocardial infarction. At relatively modest concentrations, Uric Acid crystalizes and these small crystals can damage the inner lining of the arteries, destroying the lining called the Glycocalyx.

Elevated uric acid levels can induce oxidative stress and inflammation in endothelial cells, impairing nitric oxide bioavailability and promoting vascular stiffness. These mechanisms establish a direct pathophysiological link between uric acid and cardiovascular risk (Becker & Jolly, 2006).

What Uric Acid level seems to be the threshold for causing heart disease? This is where the fun begins.

Numerous epidemiological studies have shown a correlation between elevated SUA levels and an increased risk of coronary artery disease and heart attacks. A meta-analysis of over 16 studies involving more than 200,000 participants found that individuals with hyperuricemia had a 20-40% higher risk of coronary heart disease compared to those with normal SUA levels (Li et al., 2014).

The risk of heart disease increases and the risk of serious damage begins at the level of 5.5 mg/dl. This is well below the level seen as 'high' or consistent with Gout. (please see my other Blog on Uric Acid for the data & reference)

This association remained significant even after adjusting for traditional cardiovascular risk factors such as hypertension, diabetes, and hyperlipidemia.

The role of uric acid as an independent risk factor for heart attacks has been debated, partly because hyperuricemia often coexists with other metabolic disorders. For instance, hyperuricemia is frequently associated with hypertension, insulin resistance, and obesity, all of which are established cardiovascular risk factors (Feig et al., 2008). While these conditions may confound the relationship, experimental evidence supports a direct role for uric acid in cardiovascular pathophysiology.

Uric acid has also been linked to the activation of the renin-angiotensin-aldosterone system (RAAS) and increased production of inflammatory cytokines, further exacerbating cardiovascular risk. Elevated SUA levels can lead to renal microvascular damage, promoting hypertension—a well-known risk factor for myocardial infarction (Mazzali et al., 2001). This interaction highlights the systemic impact of hyperuricemia on cardiovascular health.

Clinical studies have suggested that reducing uric acid levels through pharmacological interventions, such as allopurinol or febuxostat, may mitigate cardiovascular risk. For instance, a randomized controlled trial found that allopurinol improved endothelial function and reduced arterial stiffness in patients with hyperuricemia (Kanbay et al., 2011). While these findings are promising, further research is needed to confirm the cardiovascular benefits of uric acid-lowering therapy.

Gender differences in the relationship between uric acid and cardiovascular risk have also been observed. Women, particularly premenopausal women, appear to have a weaker association between hyperuricemia and heart attacks compared to men, possibly due to the uricosuric effects of estrogen. However, postmenopausal women show a similar risk profile to men, underscoring the complex interplay between sex hormones and uric acid metabolism (Chen et al., 2015).

Hyperuricemia has also been associated with the formation of microvascular thrombi, which can contribute to acute coronary syndromes. Uric acid crystals can activate the NLRP3 inflammasome, leading to the release of interleukin-1β and subsequent inflammatory cascades that destabilize atherosclerotic plaques (Martinon et al., 2006). These processes further elucidate the mechanistic link between uric acid and myocardial infarction.

Despite the growing evidence, some experts argue that uric acid may serve more as a marker of cardiovascular risk rather than a causative factor. This perspective emphasizes the need for well-designed longitudinal studies and clinical trials to disentangle the complex relationship between SUA levels and heart attacks (Kuwabara et al., 2018).

In conclusion, elevated uric acid levels are strongly associated with an increased risk of heart attack through multiple mechanisms, including endothelial dysfunction, oxidative stress, and inflammation. While hyperuricemia is often intertwined with other cardiovascular risk factors, it may also independently contribute to myocardial infarction.

Addressing hyperuricemia through lifestyle modifications and pharmacological interventions could potentially reduce cardiovascular risk, but further research is essential to validate these strategies.

What can I realistically do to address this potential problem?

1. Get your uric acid level checked regularly. At my practice, Stages of Life Medical Institute, we check our patients every 3 to 6 months.

   
   

2. Maintain your level below 5.4

   
   

3. My preferred medication is Allopurinol. Starting dosage is 100 mg tablet, 2 in the morning. Titrate the dosage upward after subsequent blood work confirms the level and suggests a change, usually an increase in dosage.

   
   

4. Eat sensibly. Go to your favorite search engine and read about what foods are good for patients with gout, and you are well on your way to getting this under control.

   
   

5. In my practice, I have found that the CRP levels, used to look for inflammation decrease substantially when the uric acid levels are lowered below 4.2 mg/dl.

   
   

References

1. Becker, M. A., & Jolly, M. (2006). Hyperuricemia and associated diseases. Rheumatic Disease Clinics of North America, 32(2), 275-293.

2. Li, M., Hou, W., Zhang, X., Hu, L., Tang, Z., & Wang, C. (2014). Hyperuricemia and risk of stroke: a systematic review and meta-analysis of prospective studies. Atherosclerosis, 232(2), 265-270.

3. Feig, D. I., Kang, D. H., & Johnson, R. J. (2008). Uric acid and cardiovascular risk. New England Journal of Medicine, 359(17), 1811-1821.

4. Mazzali, M., Hughes, J., Kim, Y. G., et al. (2001). Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension, 38(5), 1101-1106.

5. Kanbay, M., Ozkara, A., Selcoki, Y., et al. (2011). Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearance, and proteinuria in patients with normal renal functions. International Urology and Nephrology, 39(4), 1227-1233.

6. Chen, L., Zhu, W., & Chen, Z. (2015). Gender and age specific prevalence of hyperuricemia and its associated risk factors in Chinese adults: A longitudinal study. BMC Public Health, 15(1), 537.

7. Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006). Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature, 440(7081), 237-241.

8. Kuwabara, M., Niwa, K., Nishi, Y., et al. (2018). Relationship between serum uric acid levels and cardiovascular disease risk factors in a Japanese cohort. Journal of Cardiology, 71(3), 283-288.

9. Borghi, C., & Cicero, A. F. G. (2016). Serum uric acid and cardiovascular risk: state of the art and future perspectives. Current Cardiology Reports, 18(2), 118.

10. Gagliardi, A. C., Miname, M. H., & Santos, R. D. (2009). Uric acid: A marker of increased cardiovascular risk. Atherosclerosis, 202(1), 11-17.

David S. Klein, MD FACA FACPM

David S. Klein, MD, FACA, FACPM

1917 Boothe Circle

Longwood, Florida 32750

Tel: 407-679-3337

Fax: 407-678-7246