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Author: Jeet Saha

NAD and age-related diseases

What is NAD?

Nicotinamide adenine dinucleotide (NAD) is a necessary molecule for maintaining life and is found in every cell. NAD is involved in redox reactions and comes in two forms: NAD+ and NADH. Insufficient NAD is involved in five out of the nine hallmarks of aging and can increase the risks of age-related diseases such as cancer, stroke, heart disease, diabetes, and neurodegenerative diseases.

Energy metabolism

NAD is necessary for major energy pathways such as glycolysis, the Krebs cycle, and oxidative phosphorylation. All of these pathways produce the body’s energy currency: ATP. When NAD is not available, cells can’t produce enough ATP to sustain important biological processes which leads to suboptimal health.

Sirtuins: aging regulators

Sirtuins are enzymes that require NAD+ to function and are involved in five hallmarks of aging. When there are healthy amounts of sirtuins and NAD+ cofactors, they inhibit the hallmarks: epigenetic alterations, mitochondrial dysfunction, deregegulated nutrient sensing, genomic instability, and cellular senescence.

DNA repair

The PARP enzymes use NAD to repair DNA to prevent genomic instability, a hallmark of aging.

The sirtuin enzymes also help prevent genomic instability by helping FOXO transcription factors to bind to DNA and express antioxidant enzymes to protect cells from oxidative stress.

NAD deficiency accelerates the hallmarks of aging

When the body does not have enough NAD, all of the above roles are harmed. Without enough NAD, genomic instability, epigenetic alterations, deregulated nutrient sensing, and poor energy metabolism hurt wellness and promote aging. NAD declines with age because it is consumed by enzymes, mainly CD38.

Hallmarks of aging affected by NAD
Hallmark Description NAD’s role
Epigenetic alteration Each of you cells share the same DNA. Epigenetics is what decides which pieces of DNA to use to make proteins and is the reason we have different cell types. With age, our cells become confused and lose some of their ability to function properly within their cell types.
Loss of proteostasis Proteostasis is the ability of a cell to make stable, functioning proteins. As we age, some cells lose the ability to do this well. Instead, they make ineffective or harmful proteins.
Mitochondrial dysfunction Mitochondria generate energy in the form of the ATP molecule via the Krebs cycle and oxidative phosphorylation. These processes are called respiration and produce free radicals that can harm the cell in large numbers. As we age our mitochondria become dysfunctional by producing less ATP and more free radicals.
Senescence Senescent cells are those that stop dividing. This is a good mechanism for preventing cancer, but it can be harmful because it causes cells to release inflammatory molecules into the body and contribute to chronic inflammation.
Deregulated nutrient sensing Cells respond to the availability of nutrients in the diet through different pathways. When nutrient sensing is deregulated, cells don’t respond well to nutrients which can lead to conditions such as insulin insensitivity.

What are the risk factors for NAD deficiency?

NAD declines with age and contributes to disease

Obesity is also a risk factor for NAD depletion, possibly because it contributes to chronic inflammation, which causes DNA damage, requires NAD+-consuming PARP hyperactivation.

NAD deficiency is a common central pathological factor of a number of diseases and aging: cerebral ischemia, myocardial ischemia, diabetes, cancer, metabolic, neurodegenerative diseases, and other age-associated pathologies.

How can you optimize your NAD levels?

Supplementation

NAD precursor supplements such as NR and NMN have been shown to raise NAD levels in humans.

Diet and exercise

Obesity is associated with reduced expression of NAD and sirtuins, whereas weight loss increases NAD and sirtuin expression.

Exercise has been shown to increase activity of an NAD-synthesizing enzyme called NAMPT.

NAD pathways
Reprinted from “Srivastava S. Emerging therapeutic roles for NAD(+) metabolism in mitochondrial and age-related disorders. Clin Transl Med. 2016;5(1):25. doi:10.1186/s40169-016-0104-7”

Antioxidants and the TAC assay

Article topics

What is TAC?

Our total antioxidant capacity (TAC) test measures the ability of the blood to blunt the harmful effects of oxidative stress. Although it does not include all of the body’s antioxidant defenses like intracellular enzymes such as superoxide dismutase, it provides a valuable measure of a person’s antioxidant capacity that can be used to identify antioxidant deficiencies and to guide to optimal levels.

Antioxidants blunt the effects of oxidative stress by stopping free radicals from damaging cellular DNA, proteins, and lipids. Stopping free radicals improves immune function, increases healthspan, and reduces DNA damage that contributes to cancer and aging. Combined with the d-ROMs assay, TAC provides a picture of how well you are protected from the harmful effects of oxidative stress.

antioxidants and free radicals
Antioxidants donate electrons to free radicals and stop cell damage.

What are the risk factors for antioxidant deficiency?

Environmental and internal stresses that produce free radicals deplete the body’s antioxidant stores. If you chronically expose yourself to stressors like pollution or a an inflammatory diet, then you will overuse your antioxidant reserves and risk becoming deficient.

Some causes of antioxidant deficiencies:

  • Diets low in antioxidants
  • Alcohol
  • Smoking
  • Radiation
  • Pollution
  • Infections
  • Obesity
  • Chronic inflammation
  • Excessive iron, magnesium, copper, or zinc
  • Excessive antioxidant supplementation

How can you optimize your antioxidant levels?

A word of caution on supplements

While reducing oxidative stress is a good thing, heavy use of supplements like over-the-counter vitamin C and vitamin E can be harmful. In a meta-analysis of 14 clinical trials (n=170,525), antioxidant supplementation was not found to prevent gastrointestinal cancer, but may have increased risk instead.

Many more studies on antioxidant supplementation failed to find beneficial effects:

  • A meta-analysis of 19 randomized clinical trials (n=135,967) concluded that high-dose vitamin E supplements may increase all-cause mortality.
  • A meta-analysis of 53 randomized trials (n=241,833) found an increased risk of all-cause mortality after supplementing with antioxidants.

Diet

Contrary to supplemental antioxidants, dietary antioxidants have a positive effect on health. A study (n=521,457) on the effects of dietary antioxidant compounds found a reduced risk of gastric cancer. Another study surveyed cancer patients and controls suggests eating antioxidant-rich whole foods lowers the risk of cancers like non-Hodgkin’s lymphoma.

Why might whole foods have an effect on cancers while individual supplements may not? The answer may be that there is a synergistic antioxidant effect from eating whole foods that lowers the risks of developing age-related diseases.

Aside from mortality risk, antioxidants can improve cognitive ability. Lutein and zeaxanthin are antioxidants that cross the blood-brain barrier and reduce oxidative stress in the brain. They are found in green leafy vegetablesand can improve cognitive function in older adults

A diverse, non-exhaustive list of high antioxidant foods:

  • Beverages
    • Green tea
    • Coffee
    • Red wine
  • Nuts
    • Walnuts
    • Sunflower seeds
  • Berries, fruits, and vegetables
  • Spices and herbs
    • Cloves
    • Oregano
    • Thyme
antioxidant foods diet

Conclusion

Antioxidants are an integral part of a healthy diet. If you believe you are deficient, try adding more some spices into your meals like allspice, oregano, or cloves, and increase your intakes of fruits and vegetables. Try to get all your antioxidants from whole foods if possible. If you have an allergy to fruits and find it difficult to take in antioxidants from whole foods or spices, then consider small-dose supplements while monitoring your biomarkers so you don’t take high doses.

References

  • Tan BL, Norhaizan ME, Liew WP, Sulaiman Rahman H. Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases. Front Pharmacol. 2018;9:1162. Published 2018 Oct 16. doi:10.3389/fphar.2018.01162
  • Singh AK, Pandey P, Tewari M, Pandey HP, Gambhir IS, Shukla HS. Free radicals hasten head and neck cancer risk: A study of total oxidant, total antioxidant, DNA damage, and histological grade. J Postgrad Med. 2016;62(2):96-101. doi:10.4103/0022-3859.180555
  • Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13:757-772. Published 2018 Apr 26. doi:10.2147/CIA.S158513
  • Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004;364(9441):1219-1228. doi:10.1016/S0140-6736(04)17138-9
  • Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37-46. doi:10.7326/0003-4819-142-1-200501040-00110
  • Bjelakovic G, Nikolova D, Gluud C. Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm?. PLoS One. 2013;8(9):e74558. Published 2013 Sep 6. doi:10.1371/journal.pone.0074558
  • Serafini M, Jakszyn P, Luján-Barroso L, et al. Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study. Int J Cancer. 2012;131(4):E544-E554. doi:10.1002/ijc.27347
  • Holtan SG, O’Connor HM, Fredericksen ZS, et al. Food-frequency questionnaire-based estimates of total antioxidant capacity and risk of non-Hodgkin lymphoma. Int J Cancer. 2012;131(5):1158-1168. doi:10.1002/ijc.26491
  • Liu RH. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr. 2003;78(3 Suppl):517S-520S. doi:10.1093/ajcn/78.3.517S
  • Eisenhauer B, Natoli S, Liew G, Flood VM. Lutein and Zeaxanthin-Food Sources, Bioavailability and Dietary Variety in Age-Related Macular Degeneration Protection. Nutrients. 2017;9(2):120. Published 2017 Feb 9. doi:10.3390/nu9020120
  • Hammond BR Jr, Miller LS, Bello MO, Lindbergh CA, Mewborn C, Renzi-Hammond LM. Effects of Lutein/Zeaxanthin Supplementation on the Cognitive Function of Community Dwelling Older Adults: A Randomized, Double-Masked, Placebo-Controlled Trial. Front Aging Neurosci. 2017;9:254. Published 2017 Aug 3. doi:10.3389/fnagi.2017.00254
  • Carlsen MH, Halvorsen BL, Holte K, et al. The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide. Nutr J. 2010;9:3. Published 2010 Jan 22. doi:10.1186/1475-2891-9-3
  • Zhao T, Sun Q, Marques M, Witcher M. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry). Oxid Med Cell Longev. 2015;2015:950890. doi:10.1155/2015/950890

Vitamin D

What is vitamin D?

The main role of vitamin D is to maintain healthy bones by helping calcium and phosphate absorption from the intestines. Not having enough vitamin D raises risk of bone loss and fractures. Vitamin D is likely beneficial for other parts of the body as well. Studies have suggested an overall decrease in death, cancer, heart disease, blood pressure, respiratory illnesses, depression, chances of having a low-birthweight baby.

Vitamin D helps the immune system stay balanced. The way that vitamin D keeps the immune system healthy is very complex. Too much immune stimulation can result in autoimmune diseases. Insufficient immune system activity can result in frequent infections. A large prospective clinical trial showed in 2017 that vitamin D reduces the odds of developing a respiratory infection by approximately 42% in people with low baseline levels of 25-hydroxyvitamin D (< 25 ng/mL). Recent studies suggest that vitamin D plays a critical role in reducing COVID-19 infection and helping recovery from COVI-19 infection.

How to act on the result on Vitamin D has been the subject of great controversy in the medical field. Blood level of 25-hydroxy-vitamin D is usually measured in nanograms per milliliter. One opinion on the vitamin D deficiency is less than 12.5 ng/mL, which is found in about 6% of Americans. The Institute of Medicine (IOM) estimated that a vitamin D level of 20 ng/mL or higher was adequate for good bone health, and subsequently a level below 20 was considered a vitamin D deficiency. In 2011, the Endocrine Society issued a report urging a much higher minimum blood level of vitamin D. It concluded that “at a minimum, we recommend vitamin D levels of 30 ng/mL, and because of the vagaries of some of the assays, to guarantee sufficiency, we recommend between 40 and 60 ng/mL for both children and adults.”

Excessive supplementation of vitamin D may be harmful. Vitamin D is stored in fat and your fat cells can only store so much vitamin D. The result of high levels of vitamin D is high levels of calcium in blood and potentially hypercalcemia and calcification. Too high levels of vitamin D can be immunosuppressive as well.

What are the causes of vitamin D deficiency?

While anyone can be deficient in vitamin D, people who are older, have darker skin, or do not get enough sunlight are more likely to be deficient in vitamin D. People with certain diseases such as cancer often have vitamin D deficiency.

Intervention tips

The main source of vitamin D is production by your body when the skin is exposed to sun. It is estimated that 1000 -1500 hours of sun exposure in the year are needed by most people to produce the necessary amount of vitamin D. Due to vigilant sun protection and other factors, vitamin D deficiency is very common and on the rise. Vitamin D can also be obtained from other sources including some natural foods such as fatty fish, egg yolks, cheese and beef liver as well as foods fortified with vitamin D such as dairy products, soymilk, and cereals. However, many people, especially older adults, people with darker skin and limited sun exposure and overweight, cannot get enough vitamin D from sun exposure and foods and require vitamin D supplements. While a daily supplement of 1000 IU may be sufficient for most people, much higher dose is necessary for those who are deficient in vitamin D level.

Too much vitamin D (>100 ng/ml) can be harmful, increasing risk for fractures, falls and kidney stones, and can be toxic due to excessive level of calcium. There is some evidence that high levels of vitamin D may be associated with certain cancers and mortality. Testing for blood vitamin D level is the best way to find out how much supplementation is needed for each person. We recommend an optimal vitamin D level between 50-80ng/mL to maximize health and longevity.

Further reading

  1. Emily S. Ruiz, M. (2020). Vitamin D: Finding a balance – Harvard Health Blog. Retrieved 24 November 2020, from https://www.health.harvard.edu/blog/vitamin-d-finding-balance-2017072112070
  2. Vitamin D Boosts the Immune System. (2020). Retrieved 24 November 2020, from https://www.pharmacytimes.com/news/vitamin-d-helps-the-immune-system-during-cold-and-flu-season
  3. New research shows a surprising link between coronavirus and vitamin D. (2020). Retrieved 24 November 2020, from https://www.mic.com/p/coronavirus-vitamin-d-the-surprising-link-according-to-new-research-40564785
  4. Vitamin D supplements are immunosuppressive | Microbe Minded. (2020). Retrieved 24 November 2020, from http://microbeminded.com/vitamin-d-supplements-are-immunosuppressive/

SA-β-gal and senescence

What is SA-β-gal?

SA-β-gal is an enzyme and considered the best biomarker for cellular senescence, which is the permanent arrest of cell growth. Senescence increases as we age and is one of the most important hallmarks of aging. Senescent cells are “zombie” cell that do not work properly, thereby negatively impacting health. Senescent cells are characterized by morphological and metabolic changes, chromatin reorganization, altered gene expression, and a pro-inflammatory phenotype known as the senescence-associated secretory phenotype (SASP). SASP proteins secreted by senescent cells, especially inflammatory cytokines, play a causative role in aging and all age-related diseases such as cancer, diabetes, atherosclerosis, osteoarthritis and infectious diseases.

Senescent cells may play a protective role because the right amount of inflammation and senescence signal for regeneration factors, and it plays a role in contributing to normal development, cell plasticity and tissue repair, as a dynamic and tightly regulated cellular program.

While senescence can be measured in cells and tissues by a variety of biomarkers and methodologies, Jinfiniti Precision Medicine offers the first commercially available senescence test for serum or plasma. The senescence biomarker measured in blood should reflect senescence level in the whole body or pathological sites. While the precise cutoff values remain to be determined, the recommended cutoffs are based on analyses of several thousand persons without obvious diseases as well as thousands of patients with various diseases and conditions including cancer and diabetes.

Risk factors and how senescent cells cause harm

Cellular senescence can be triggered by a number of cellular stresses, including oxidative stress, telomere dysfunction, non-telomeric DNA damage, epigenetic repression of the INK4a/ARF locus, and oncogenic activation among others. Poor lifestyle choices, like lack of exercise and overeating, can contribute to cellular senescence.

Intervention tips

A healthy lifestyle including exercise can help prevent the formation of senescent cells. Likewise, intermittent fasting has been shown in animal models to promote autophagy, or cellular “self-eating” that helps clear out damaged cellular components including mis-folded proteins.

Senolytics are drugs that can reduce or eliminate senescent cells. A number of flavonoids, particularly fisetin, have been shown to have senolytic activity. Emerging natural compounds have been discovered to be effective senolytic agents, such as quercetin, fisetin, piperlongumine and the curcumin analog. The combination of dasatinib (an anti-cancer drug) plus quercetin (a flavonoid supplement), have been shown to decrease senescent cells in humans.

The SA-β-galactosidase test gives you a picture of your cellular senescence and will help you and your medical professional evaluate your level of senescence.

Further reading

  1. Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., Kleijer, W. J., DiMaio, D., & Hwang, E. S. (2006). Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging cell, 5(2), 187–195. https://doi.org/10.1111/j.1474-9726.2006.00199.x
  2. Fuhrmann-Stroissnigg, H., Santiago, F. E., Grassi, D., Ling, Y., Niedernhofer, L. J., & Robbins, P. D. (2019). SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs. Journal of visualized experiments : JoVE, (148), 10.3791/58133. https://doi.org/10.3791/58133
  3. Dolgin E. (2020). Send in the senolytics. Nature biotechnology, 10.1038/s41587-020-00750-1. Advance online publication. https://doi.org/10.1038/s41587-020-00750-1
  4. Overview of Cellular Senescence and Aging | Cell Signaling Technology. (2020). Retrieved 24 November 2020, from https://www.cellsignal.com/contents/_/cellular-senescence/overview-of-cellular-senescence
  5. Freund, A., Orjalo, A. V., Desprez, P. Y., & Campisi, J. (2010). Inflammatory networks during cellular senescence: causes and consequences. Trends in molecular medicine, 16(5), 238–246. https://doi.org/10.1016/j.molmed.2010.03.003
  6. Rhinn, M., Ritschka, B., & Keyes, W. M. (2019). Cellular senescence in development, regeneration and disease. Development (Cambridge, England), 146(20), dev151837. https://doi.org/10.1242/dev.151837
  7. Don’t Be a Zombie: Senolytics, Exercise and Fasting Fight Off Senescent Cells. (2020). Retrieved 24 November 2020, from https://medium.com/lifeomic/dont-be-a-zombie-senolytics-exercise-and-fasting-fight-off-senescent-cells-cc720d88240
  8. Yousefzadeh, M. J., Zhu, Y., McGowan, S. J., Angelini, L., Fuhrmann-Stroissnigg, H., Xu, M., Ling, Y. Y., Melos, K. I., Pirtskhalava, T., Inman, C. L., McGuckian, C., Wade, E. A., Kato, J. I., Grassi, D., Wentworth, M., Burd, C. E., Arriaga, E. A., Ladiges, W. L., Tchkonia, T., Kirkland, J. L., … Niedernhofer, L. J. (2018). Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 36, 18–28. https://doi.org/10.1016/j.ebiom.2018.09.015
  9. Li, W., Qin, L., Feng, R., Hu, G., Sun, H., He, Y., & Zhang, R. (2019). Emerging senolytic agents derived from natural products. Mechanisms of ageing and development, 181, 1–6. https://doi.org/10.1016/j.mad.2019.05.001
  10. Hickson, L. J., Langhi Prata, L., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., Herrmann, S. M., Jensen, M. D., Jia, Q., Jordan, K. L., Kellogg, T. A., Khosla, S., Koerber, D. M., Lagnado, A. B., Lawson, D. K., LeBrasseur, N. K., Lerman, L. O., McDonald, K. M., McKenzie, T. J., Passos, J. F., … Kirkland, J. L. (2019). Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine, 47, 446–456. https://doi.org/10.1016/j.ebiom.2019.08.069

Oxidative stress

Oxidative stress

Oxidative stress (OS) is a phenomenon or physiological state caused by the imbalance between free radicals and antioxidants in your body. Free radicals, all called reactive oxygen species (ROS) or reactive oxygen metabolites (ROM) are oxygen-containing molecules with an uneven number of electrons, allowing them to easily react with other molecules. ROS are constantly produced by mitochondria in your cells as part of the physiological processes to produce energy and some pathological conditions. They can play, and in fact they do play, several physiological roles (i.e., cell signaling). Several biological functions, such as like protein phosphorylation, apoptosis, immunity, and differentiation, are all dependent on a proper and low level of ROS. However, ROS production can be greatly increased by environmental stressors (UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (antiblastic drugs). ROS are detoxified by antioxidants such as vitamin C, vitamin E, flavonoids, and polyphenols from your foods or supplements. Excessive production of ROS and/or insufficient intake or detoxifying antioxidants cause the imbalance and. Excessive ROS are harmful to your body because they damage your cell’s DNA, proteins, and lipids, causing cell and tissue damage. Oxidative stress is one of the most important underlying causes of aging and aging-related diseases.

What is ROM?

Reactive metabolites (ROM), reactive oxygen species (ROS), or sometimes simply called oxidants, comprise a number of oxygen-containing molecules such as superoxide radicals (O2•−), hydrogen peroxide (H2O2), hydroxyl radicals (•OH), and singlet oxygen (1O2). ROS are natural byproducts of oxygen metabolism in the mitochondria. At low concentrations, ROS help fight pathogens and synthesize cellular structures. ROS can play an important role in some cell signaling pathways. When ROS production is too high, they can cause severe damages to DNA, RNA, lipids, and especially proteins and cell membrane. A large body of evidence shows that oxidative stress can be responsible, with different degrees of importance, for the onset and/or progression of many diseases (i.e., cancer, diabetes, metabolic disorders, atherosclerosis, and cardiovascular diseases).

It is widely known that large amounts of oxidants accelerate aging. However, a recent study has shown that oxidants may have some positive functions such as slowing down cell aging, raising the possibility that some oxidants, at adequate levels, may play a role in health and longevity.

Various individual ROS can be measured by laboratory test. The ROM test measures all reactive oxygen metabolites and is therefore a great assessment for the overall status for oxidative stress.

What are the risk factors for high ROM?

Causes of high ROM
  • High fat and sugar diet.
  • Alcohol.
  • Chronic inflammation.
  • Smoking.
  • UV.
  • Ionizing radiation.
  • Pollutants.
  • Heavy metals.

Intervention tips

How to lower oxidative stress
  • Healthy diet: low fat and sugar.
  • Eat a diet rich in antioxidants.
  • Caloric restriction and intermittent fasting.
  • Exercise.
  • Avoid environmental stress.
  • Supplements can increase enzymes with ROM-neutralizing functions: resveratrol, turmeric, green tea, grapeseed, cocoa, chokeberry.
  • Antioxidant supplements: vitamin C, vitamin E, glutathione, and more.

Further reading

  1. Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., & Bitto, A. (2017). Oxidative Stress: Harms and Benefits for Human Health. Oxidative medicine and cellular longevity, 2017, 8416763. https://doi.org/10.1155/2017/8416763
  2. Saha, S. K., Lee, S. B., Won, J., Choi, H. Y., Kim, K., Yang, G. M., Dayem, A. A., & Cho, S. G. (2017). Correlation between Oxidative Stress, Nutrition, and Cancer Initiation. International journal of molecular sciences, 18(7), 1544. https://doi.org/10.3390/ijms18071544
  3. Uttara, B., Singh, A. V., Zamboni, P., & Mahajan, R. T. (2009). Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Current neuropharmacology, 7(1), 65–74. https://doi.org/10.2174/157015909787602823
  4. Masaki, N., Sato, A., Horii, S., Kimura, T., Toya, T., Yasuda, R., Namba, T., Yada, H., Kawamura, A., & Adachi, T. (2016). Usefulness of the d-ROMs test for prediction of cardiovascular events. International journal of cardiology, 222, 226–232. https://doi.org/10.1016/j.ijcard.2016.07.225
  5. Oxidants can slow down the cell ageing. (2020). Retrieved 24 November 2020, from https://www.techexplorist.com/oxidants-slow-down-cell-ageing/36060/
  6. Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A. (2020). Retrieved 24 November 2020, from https://elifesciences.org/articles/60346
  7. Natural Remedies for Fighting Oxidative Stress. (2020). Retrieved 24 November 2020, from https://www.verywellhealth.com/oxidative-stress-and-your-health-89492
  8. Antioxidants Explained in Simple Terms. (2020). Retrieved 24 November 2020, from https://www.healthline.com/nutrition/antioxidants-explained#supplements

LDL-C

What is LDL?

The liver produces cholesterol that your body needs and packages fat molecules (cholesterol, phospholipids, and triglycerides) in very low-density lipoproteins (VLDL). As VLDL transports fat to cells around your body, VLDL becomes low-density lipoproteins (LDL), the more dense particle. LDL delivers fat wherever it is needed. LDL is the “bad” cholesterol that are prone to damage by free radicals through a process called oxidization within the walls of arteries. Oxidized LDL is even more harmful to health, raising the risk of atherosclerosis, heart attack or stroke.

Our blood test reports LDL-C, the average amount of cholesterol estimated to be contained within LDL particles. LDL-C is calculated by measuring total cholesterol, HDL-C, and triglycerides. For patients with triglycerides more than 400, LDL-C test is not accurate. Other conditions such as severe cirrhosis also make the test inaccurate. For persons with high LDL-C, measuring oxidized LDL, a more expensive test, can provide better estimate for disease risk.

Risks associated with high LDL levels

  • Coronary artery disease.
  • Peripheral artery disease.
  • Heart disease.
  • Stroke.

Intervention tips for lowering LDL

There are many natural ways to lower your cholesterol levels when they are borderline high but medications may be required when your cholesterol levels are high.

If your cholesterol is high, please consult with a physician to choose the best intervention for you.

  • Healthy diet.

    • Avoid high saturated and trans fats, cholesterol, or simple carbs.
    • Eat monounsaturated fats from foods like olives and olive oil, canola oil, nuts, pecans, and avocados
    • Use polyunsaturated fats, especially omega-3s.
    • Eat more soluble fiber and probiotics to promote gut health.
    • Consider plant sterols and stanols (plant cholesterol) naturally found in vegetable oils.
  • Cholesterol-lowering supplements.

    • Omega-3 supplements.
    • Niacin (vitamin B3).
    • Psyllium: a form of soluble fiber.
    • Coenzyme Q10.
  • Lifestyle changes.

    • No smoking.
    • Regular exercise.
    • Lose weight.
    • Reduce alcohol consumption.
  • Control high blood pressure and diabetes.
  • Medications.

    • Statins to reduce cholesterol production.
    • Niaspan: a niacin-based prescription drug with high potency.
    • Zetia to lower absorption of dietary cholesterol.
    • Probucol and vitamin E to prevent LDL oxidation and atherosclerosis.

Further reading

  1. Wikipedia contributors. (2020, November 20). Low-density lipoprotein. In Wikipedia, The Free Encyclopedia. Retrieved 18:56, November 25, 2020, from https://en.wikipedia.org/w/index.php?title=Low-density_lipoprotein&oldid=989643886
  2. WebMD. 2020. LDL Cholesterol. [online] Available at: [Accessed 25 November 2020].
  3. 10 Natural Ways to Lower Your Cholesterol Levels. (2020). Retrieved 25 November 2020, from https://www.healthline.com/nutrition/how-to-lower-cholesterol
  4. Publishing, H. (2020). On call: Niacin for cholesterol – Harvard Health. Retrieved 25 November 2020, from https://www.health.harvard.edu/newsletter_article/on-call-niacin-for-cholesterol

hs-CRP

What are CRP and hs-CRP?

C-reactive protein (CRP) is a substance that the liver makes in response to inflammation. The C-reactive protein test measures the amount of this protein in the blood. The test can help to diagnose acute and chronic conditions that cause inflammation. A wide variety of inflammatory conditions can cause elevated CRP levels, including infection, organ and tissue injury, cancer, obesity, autoimmune conditions, pericarditis. Very high CRP levels (>350mg/L) are almost always a sign of a serious underlying medical condition, likely a severe infection or a poorly controlled autoimmune disease or severe tissue damage.

The high sensitivity CRP (hs-CRP) test is different from the CRP test. The hs-CRP test detects lower levels of CRP in the bloodstream (0-10mg/L), while the CRP test measures levels in the 10-1,000mg/L range. The hs-CRP test is used to evaluate chronic inflammation and a person’s risk of developing diseases and conditions such as cardiovascular disease, atherosclerosis, diabetes and sedentary lifestyle.

There is currently no definitive standard for CRP blood levels, and guidelines vary. As a general rule, the following thresholds apply:

  • Normal levels are below 1 mg/L.
  • Slightly elevated levels (1 – 3 mg/L) indicate a moderate risk of developing cardiovascular disease and perhaps other diseases.
  • Moderately elevated levels (3 – 10 mg/L) are usually result from chronic conditions such as diabetes, hypertension, obesity, tobacco smoking and sedentary lifestyle.
  • Highly elevated levels (10 – 100 mg/L) are usually due to significant inflammation from an infectious or non-infectious cause.
  • Extremely high levels (above 100 mg/L) are almost always a sign of severe bacterial, fungal or viral infection, and sometimes cancer.

What are the most likely cause of elevated CRP?

A huge range of diseases and conditions can raise CRP levels, making the determination of the exact cause of its elevation almost impossible by looking at CRP levels alone. However, the causes fall into the following categories:

  • Viral, bacterial or fungal infection including COVID-19.
  • Injury, surgery or wound.
  • Cancer.
  • Chronic diseases: diabetes, obesity, hypertension, cardiovascular disease, arthritis, pericarditis and autoimmune diseases.
  • Lifestyle conditions: overweight, sedentary lifestyle.
  • Estrogen levels: Estrogen-based medications such as birth control pills and hormone replacement medications.
  • Pregnancy: especially during the later stages.

Intervention tips

You should consult a doctor and find out the cause if you have high levels of CRP (>10mg/L). For slightly (1-3mg/L) to moderately elevated levels (3-10mg/L), you should monitor it changes over time and potentially take actions to reduce the levels. There are many different supplements that can help reduce chronic inflammation and the commonly used supplements include curcumin contained in turmeric, alpha-lipoic acid, fish oil, ginger, resveratrol, spirulina, S-adenosylmethionine, zinc, green tea, frankincense, cat’s claw, capsaicin, andrographis and many others. Anti-inflammatory supplements do not work for everyone and you should find out which one(s) work the best for you. In almost all cases, supplements take time to reverse inflammation.

Medications may be needed to reduce inflammation in the body when it is highly elevated. Specific nonsteroidal anti-inflammatory drugs (NSAIDs) and some cholesterol-reducing medicines (statins) and may help lower CRP levels.

Further reading

  1. C-reactive protein (CRP) test: High levels, low levels, and normal range. (2020). Retrieved 24 November 2020, from https://www.medicalnewstoday.com/articles/322138
  2. 6 Supplements That Fight Inflammation. (2020). Retrieved 24 November 2020, from https://www.healthline.com/nutrition/6-anti-inflammatory-supplements
  3. Anti-inflammatory supplements: 8 natural options. (2020). Retrieved 24 November 2020, from https://www.medicalnewstoday.com/articles/326067

HDL-C

What is HDL?

Unlike the “bad” low-density lipoprotein particles (LDL) which deliver fat molecules to cells, HDL is the “good” cholesterol that removes extra cholesterol from cells and reduces plaque buildup in your arteries and carries extra cholesterol back to your liver where it is expelled. The good balance between HDL and LDL helps reduce your risk of atherosclerosis, heart disease, heart attack and stroke.

Our blood test reports HDL-C, the average amount of cholesterol estimated to be contained within HDL particles.

Risks for low HDL

  • Obesity.
  • Sedentary lifestyle.
  • Type 2 diabetes.
  • Unhealthy diet.
  • Inflammation.
  • Smoking.

Intervention tips for increasing HDL

Many natural ways and medications to lower your bad cholesterol (LDL) levels can also increase your good cholesterol (HDL) levels high. Lowering LDL can improve HDL/LDL ratio and reduce disease risk.

  • Healthy diet.

    • Avoid high saturated and trans fats, cholesterol, or simple carbs.
    • Eat monounsaturated fats from foods like olives and olive oil, canola oil, nuts, pecans, and avocados
    • Use polyunsaturated fats, especially omega-3s.
    • Eat more soluble fiber and probiotics to promote gut health.
    • Consider plant sterols and stanols (plant cholesterol) naturally found in vegetable oils.
  • Cholesterol-lowering supplements.

    • Omega-3 supplements.
    • Niacin (vitamin B3).
    • Psyllium: a form of soluble fiber.
    • Coenzyme Q10.
  • Lifestyle changes.

    • No smoking.
    • Regular exercise.
    • Lose weight.
    • Reduce alcohol consumption.
  • Control high blood pressure and diabetes.
  • Medications.

    • Statins to reduce cholesterol production.
    • Niaspan: a niacin-based prescription drug with high potency.
    • Zetia to lower absorption of dietary cholesterol.
    • Probucol and vitamin E to prevent LDL oxidation and atherosclerosis.

Further reading

  1. Wikipedia contributors. (2020, November 11). High-density lipoprotein. In Wikipedia, The Free Encyclopedia. Retrieved 19:18, November 25, 2020, from https://en.wikipedia.org/w/index.php?title=High-density_lipoprotein&oldid=988093461
  2. 11 Foods to Increase Your HDL. (2020). Retrieved 25 November 2020, from https://www.healthline.com/health/high-cholesterol/foods-to-increase-hdl
  3. Publishing, H. (2020). On call: Niacin for cholesterol – Harvard Health. Retrieved 25 November 2020, from https://www.health.harvard.edu/newsletter_article/on-call-niacin-for-cholesterol
  4. Kraft, A. (2020). 8 Ways to Raise HDL Cholesterol | Everyday Health. Retrieved 25 November 2020, from https://www.everydayhealth.com/high-cholesterol/living-with/how-to-raise-hdl-cholesterol/
  5. Emily M. Ambizas, N. (2020). OTC Supplements for the Management of High Cholesterol. Retrieved 25 November 2020, from https://www.uspharmacist.com/article/otc-supplements-for-the-management-of-high-cholesterol

GSP

What is GSP?

Glycation is the non-enzymatic bonding of a sugar molecule to a protein or lipid molecule. Glycated serum proteins (GSP) are proteins that have undergone glycation and circulate in the blood. The vast majority (90%) of GSP consists of glycated albumin. GSP concentration is an indication of the average amount of glucose (glycemia) in the blood over the previous two to three weeks while glycated hemoglobulin, particularly HbA1c, is a measurement of glycemia over the past two to three months. Therefore, GSP closes the information gap between daily glucose measurement and quarterly HbA1c measurement to provide a full spectrum monitoring of glycemic control for patients with diabetes. Furthermore, HbA1c may be of limited value in some situations such as pregnancy, reduced RBC lifespan and hemodialysis. GSP may be altered independent of glycemia by factors that influence albumin metabolism. Interestingly, GSP level is lower in some patients with various types of cancer and lower GSP level may be associated with poor survival in certain types of cancer, probably because of albumin deficiencies in cancer patients.

GSP are precursors of advanced glycation end-products (AGEs). AGEs contribute to a variety of microvascular and macrovascular diseases. Studies have suggested that measuring GSP and HbA1c provides a better assessment of the long term risk of developing diabetic complications.

What are the risk factors for abnormal GSP?

Diabetes and diabetic complications are the major causes for higher GSP (>290 μmol/L). Borderline GSP values may indicate increased risk of diabetes. Lifestyle factors, like diets high in sugar, fat and salt, are risk factors for increased GSP levels. Diseases or conditions with altered albumin metabolism or protein levels such as the nephrotic syndrome, cirrhosis, thyroid disease, hyperuricemia, hypertriglyceridemia, smoking, liver, thyroid, and renal diseases can alter GSP level.

Cancer may be associated with low GSP values.

Intervention tips

Besides reducing sugar intake, some ways to modify high GSPs include:

  • Exercise regularly.
  • Lose weight.
  • Control carb intake and implement portion control.
  • Increase fiber intake.
  • Drink water and stay hydrated.
  • Choose foods with a low glycemic index, which assesses the body’s blood sugar response to foods that contain carbs.
  • Reduce stress levels.
  • Monitor blood sugar levels.
  • Get enough quality sleep.
  • Eat foods rich in chromium and magnesium.
  • Food and supplements: apple cider vinegar, cinnamon extract, berberine, fenugreek seeds.
  • Test for diseases that may alter GSP levels.

Further reading

  1. Glycated albumin – utility and distinction vs A1C and fructosamine. (2020). Retrieved 24 November 2020, from https://www.mlo-online.com/disease/diabetes/article/21130617/glycated-albumin-utility-and-distinction-vs-a1c-and-fructosamine
  2. Welsh, K. J., Kirkman, M. S., & Sacks, D. B. (2016). Role of Glycated Proteins in the Diagnosis and Management of Diabetes: Research Gaps and Future Directions. Diabetes care, 39(8), 1299–1306. https://doi.org/10.2337/dc15-2727

ALT

What is ALT?

Alanine aminotransferase (ALT, also known as SGPT) is one of the most widely tested liver enzymes. The other one is aspartate aminotransferase (AST or SGOT). In healthy persons, these liver enzymes are predominantly contained within liver cells and to a lesser degree in the muscle cells. When the liver is injured or damaged, liver cells spill these enzymes into the blood stream, resulting in elevated levels of AST and ALT in the blood and indicating liver diseases. There are also other enzymes found in the liver, including alkaline phosphatase, gamma-glutamyl transpeptidase (GGT) and 5′ nucleotidase. ALT and the other liver enzyme tests are used to assess liver damages from hepatitis, infection, cirrhosis, liver cancer, or other liver diseases. Other factors including medicines, age, gender, diet, body weight, and geographical location can affect ALT results.

The normal range for ALT in blood has been an issue of debate and does vary depending on testing laboratories or medical organizations and the purpose of the assay. In healthy individuals, blood ALT levels can fluctuate 10 to 30% from one day to the next and can fluctuate 45% during a single day, with highest levels observed in the afternoon and lowest level at night. Our test population has a median value of 16 units per liter (U/L) in adults who do not have known liver diseases. This is comparable to the median value of 11 U/L for women and 13 U/L for men in a published report. For disease diagnosis purpose, the cutoff is usually set at a very high value, 63 U/L; however, ALT should be maintained in an optimum range for health management purpose. We recommend an optimum blood ALT level between 14 and 33 U/L.

Elevated ALT increases mortality risk, not only in liver disease but also in non-liver-related ailments, particularly cardiovascular disease. Mortality jumps up by 60% -80% when ALT is twice beyond the higher of the normal range.

Whereas doctors pay more attention to elevated ALT values, lower ALT in blood has been shown to be associated with lower total-body muscle mass, lower baseline fitness, increased frailty and risk of mortality in elderlies and increased risk of all-cause mortality in healthy, middle-aged and elder people. The association between ALT and mortality is inconsistent and seems particularly susceptible to age. ALT is more valuable in predicting mortality in the older population. Extremely low ALT levels appear to indicate a higher all-cause, cardiovascular-related, and cancer-related mortality.

Analysis of over 10,000 nondiabetic subjects of age 21-84 years suggested an upward surge from 21 to 64 years and a discernible steady downward decline around 65 years of age.

What are the risk factors for abnormal ALT?

Elevated ALT levels are indications of abnormal live function or damage, including non-alcoholic fatty liver disease (NAFLD), hepatitis, alcohol-related liver disease, bile duct disorders, autoimmune live disease, drug and medicine (aspirin, Tylenol, Advil, Motrin and others), and other etiology such as smoking, high cholesterol, overweight, sedent lifestyle and environmental toxins.

Causes for low ALT are not very well known. Malnutrition could be a risk factor for low ALT.

Intervention tips to lower ALT levels

If your ALT test is outside of the normal range, you should consult your doctor who may recommend a confirmatory test and/or additional tests to find out the exact cause for the abnormal finding. There also preventive actions you can take to keep your liver healthy and your ALT level within healthy range. These may include:

  • Reduce high cholesterol.
  • Have a healthy and balanced diet.
  • Exercise regularly and lose excess weight.
  • Increase folic acid intake.
  • Avoid alcohol, smoking, and environmental toxins.

Intervention tips to raise abnormally low ALT levels

There are no known remedies for rectifying lower than normal levels of ALT at this time because limited research has been devoted to the harmful effect of low ALT in the blood on health and mortality. Follow general guidelines for healthy lifestyle including balanced diet and exercise.

Further reading

  1. Alexander, W. (2020). New Recommendations Call for Standard ALT Screenings. Retrieved 24 November 2020, from https://www.hcplive.com/view/2007-01_23
  2. Alexander, W. (2020). New Recommendations Call for Standard ALT Screenings. Retrieved 24 November 2020, from https://www.hcplive.com/view/2007-01_23
  3. Liu, Z., Ning, H., Que, S., Wang, L., Qin, X., & Peng, T. (2014). Complex association between alanine aminotransferase activity and mortality in general population: a systematic review and meta-analysis of prospective studies. PloS one, 9(3), e91410. https://doi.org/10.1371/journal.pone.0091410
  4. Kim, J. W., Lee, K. J., Yang, H. R., Chang, J. Y., Moon, J. S., Khang, Y. H., & Ko, J. S. (2018). Prevalence and risk factors of elevated alanine aminotransferase among Korean adolescents: 2001-2014. BMC public health, 18(1), 617. https://doi.org/10.1186/s12889-018-5548-9
  5. How to lower ALT levels: 8 natural methods. (2020). Retrieved 24 November 2020, from https://www.medicalnewstoday.com/articles/326425
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