Are lower zinc levels a cause for concern for heart failure?

by Paul Yanzer

Heart Failure, Serum Zinc Levels, and Dietary Interventions for Success

Heart disease/heart failure is a complex topic to discuss. There are many influences and risk factors involved in the elevated risk of heart failure. There are also, in every direction one looks, differing points of view on how to best reverse elevated biomarkers associated with this risk. Commonalities of most credible sources include eating a diet rich in vegetables, fruits, unprocessed meats, and healthy fats (a whole foods diet), sleeping 8 or more hours per night, getting healthy levels of sunlight to exposed skin and eyes, and living an active lifestyle with regular bouts of high intensity exercise. Focusing on Zinc levels is just one aspect of this. Read on for more information.

A 2017 study published in the journal "BioMed Research International" took a look at 12 human trial studies meeting selected criteria with over 1400 participants. Results of the meta-analysis showed that heart failure patients had significantly lower zinc levels than control subjects. Because heart failure is one of the most frequent causes of death worldwide, it is important for the scientific community to learn more about how micronutrient imbalance is associated with it and how we can optimize our life for health and longevity. 

One theory of this relationship is due to the ratio of Zinc (Zn) to Copper (Cu). A lower Zn:Cu ratio has been observed in diseases such as rheumatoid arthritis, ischemic cardiomyopathy (ICM, narrowing of coronary arteries), and thyroid carcinoma. These skewed ratios are also observed in elderly hospitalized patients and in patients with atherosclerosis. 

So how does your Zn:Cu ratio become lower?

Nutritional Intake

Consuming Zn with phytate containing foods (see Dietary Interventions below) can blunt or negate zinc absorption. Molecules known as phytic acid (phytates) are common in many "health" foods. While there are some benefits to phytates in the diet (binding of dietary lead and other heavy metals), they bind minerals (see photo below for example of phytic acid binding of calcium, magnesium, zinc, iron). The foods most prevalent in phytic acids are cereal grains, seeds, and legumes (beans, peanuts, peanut butter). Phytate is considered to be an anti-nutrient. Interestingly, these are also all foods the main stream medical and health advisers consider to be first foods for infants and children. This puts children at risk for iron and mineral deficiencies when neural and growth development are at critical stages for these micro-nutrients. Traditional first foods, prior to our Western Diet, where things like egg yolk, liver and other organ meats, fatty fish, and other foods containing incredibly important fat soluble vitamins.

          

The ability of phytates to bind zinc is further confirmed by a study (8) that took a look at how different foods affect serum zinc levels after eating oysters (likely the best source of dietary zinc available). In the graph below, we see that serum zinc levels after eating oysters spike 3 hours after ingestion. Consuming either black beans or corn tortillas with the oysters significantly decreased the absorption of zinc. Not shown in the graph below, but shown in the study is that eating tortillas without zinc containing foods significantly DECREASED serum zinc levels from baseline.

Oxidative Stress

Zn and Cu are strictly regulated to their carriers in plasma, albumin (Alb) and ceruloplasmin (Cp), respectively. Accounting for mechanisms which promote or reduce the synthesis and secretion of both Zn-Alb and Cu-Cp is important in understanding the full story, and modulating these mechanisms is likely more important than nutritional zinc consumption. Serum Cp concentration increases rapidly during infection, trauma, and pregnancy. It's secretion is strongly linked to repair and maintenance mechanisms in the body commonly seen as one ages. So it isn't a bad thing in and of itself, but reducing the need for these mechanisms will help keep the body optimized to repair and maintain (Cu-Cp) and grow and proliferate (Zn-Alb) when needed. Living with low level inflammation and disease will leave Zn-Alb levels too low to effectively boost immune defense, increase metabolic activity and proliferation, and optimize stress response.

Oxidative stressors have been shown to unbind Zn-Alb and push free zinc into peripheral tissues, lowering serum zinc levels. This gives rise to metallothionein (MT) production which both aides in helping the body deal with oxidative stress, but also increases tumor cell proliferation (2,3). Again, an important function in the body when needed, but keeping the need lower most of the time can lead to high overall health outcomes. 

Stress also increases Cp levels to help repair the body. When we look at Cu-Cp secretion as a response to the need of cellular repair we can adjust the way we view our current approach to heart disease.

Cp is capable of oxidizing LDL-cholesterol and oxidized LDL cholesterol is commonly accepted as the cause of arterial inflammatory markers (LDL is present in the arteries and causes the release of inflammatory markers that are correlated with the presence of LDL). The common theme for treatment is then to lower serum cholesterol via a low cholesterol diet and/or Statin drugs. These recommendations are not optimal at best, and at worst are doing more harm than good. Recently, the US government Dietary Guidelines Advisory Committee, in order to remain consistent with the American Heart Association and American College of Cardiology, has stated that cholesterol is not considered a nutrient of concern for over consumption. Your liver makes more cholesterol per day than you are likely to consume. Statins block the ability of the liver to produce cholesterol, a necessary building block for hormones and normal functioning of most bodily systems. Statins also block the synthesis of CoQ10 by interfering with the production of mevalonic acid. Because CoQ10 is a key component in mitochondrial bioenergy transfer, a deficiency in CoQ10, routinely observed with statin medication usage, can result in a number of neurologic and myopathic syndromes and could even lead to statin induced myopathies.

Cp is also essential in protecting cells during stressful conditions (1,5). Both human and animal model studies have demonstrated that increased inflammatory markers decrease the ratio of Zn to Cu. Because Cp binds 80-95% of total serum copper, it is likely that higher levels of serum copper is due to the increased transcription of Cp needed for cellular repair and maintenance. 

As more research comes to light showing the protective side of cholesterol ((7) for example) one has to wonder if we have it backwards: Is cholesterol in the arteries instead a response to protect the body from inflammatory damage to the arteries? This would have major implications on our approach to medicine and disease treatment if the way the medical community looks at LDL cholesterol as the cause of inflammation vs a protective response to chronic systemic inflammation. A lot research looks at the correlation of lower LDL levels to lower cardiac events as a way to show LDL as the cause. What if we flip that and say lower cardiac events are correlated to lower LDL because of a reduced level of systemic inflammation and stressors. It would certainly support data showing higher cholesterol to be protective against mortality in the event of a heart attack. Unpublished data from the Minnesota Coronary Experiment (study of ~9400 men and women between 1968-1973) shows no benefit to lowering cholesterol to prevent cardiac events, but it did show a 22% INCREASE in mortality during a cardiac event for every 30mg/dL lowered cholesterol. This data was then compared with 5 other studies (10808 participants) which showed lowering cholesterol had no evidence of benefit to both coronary heart disease or all cause mortality. This is not to say that sky high cholesterol is a good thing (except maybe in post menopausal women), but when one compares WHO mortality data to cholesterol data from the British Heart Foundation, some interesting trends arise as seen in the graph below:   

This worldwide data shows lowest risk of all cause mortality to have cholesterol levels at about 220 mg/dL (for men) and lowest risk of cardiovascular diseases at around 210 mg/dL. While this is a correlation, we cannot derive causation assumptions from this data analysis, but what it does show is that our current understanding of cholesterol being a cause of inflammatory markers in arteries may not be correct and is worth investigating further. Even though this is just correlation, our current government approved heart health advice is also based on associations and even worse, non-human studies. Cause for concern would be high cholesterol with a diet high in refined carbohydrates, high triglycerides with high cholesterol (occurs with high insulin levels), and VLDL (fluffy LDL) cholesterol.

Pro-inflammatory markers

Pro-inflammatory markers IL-1, IL-6, and TNF-alpha (which are elevated in HF patients) are capable of increasing the proteins capable of binding plasma and tissue zinc and reducing bioavailability. Again, the response of the body to low grade, chronic inflammation is to increase the repair and maintain mechanisms (Cu-Cp as biomarker) and decrease the growth and proliferate mechanisms (Zn-Alb as biomarker). Cell proliferation is necessary for longevity of life. If the body is in a constant state of repair because of chronic inflammation, proliferation is less likely to occur. Reduction of inflammation via dietary or supplement intervention has shown time and again to reduce the risk of a multitude of diseases, including heart disease. (Flame OffUltimate Omega-3).

Hormone signaling

Insulin - Reduced insulin sensitivity and higher circulating insulin levels have been shown to reduce activity of Zn-Alb. Patients with pre-diabetes and type-2 diabetes have a lower Zn:Cu ratio and lower serum Zn in general. Insulin sensitivity becomes impaired as one ages. This is a both a cause for concern and one reason (of many) for a lower carbohydrate and higher fat/protein diet as one ages.

Glucocorticoids - Acute administration of corticosteroids have been shown to raise Cu and lower Zn. Chronically elevated levels of this hormone due to stress can keep the Zn:Cu ratio low over longer periods of time

GH and IGF-1 - Smaller night time surges in Growth Hormone and lower plasma IGF-1 as one ages give rise to lower plasma Zn as zinc is necessary for the expected growth promoting and proliferative activity of these hormones. Quality sleep, proper sunlight signaling at key hours of the day, high intensity bouts of exercise, and proper diet can optimize these hormones as one ages. NightGainz contains a form of zinc known to be highly absorpable and is delivered at night to give the body minerals needed to take advantage of key hormones released during the different phases sleep during a full night of sleep (8-9 hours).

Dietary Interventions

Optimal eating/lifestyle strategy:

As discussed in above, phytate containing foods have been shown to bind important minerals and micronutrients needed by the body for proper functioning. What is interesting is that the foods containing the highest phytate content are also the foods that whole food elimination diets, like the paleo diet, seek to remove. As unfortunate as the name "Paleo Diet" is (lets face it, ain't nobody really eating like cavemen without removing themselves from civilization) it is really a way of eating that seeks to eliminate processed foods and foods that may cause allergy and/or immune responses while still maintaining a high level of micro-nutrients and nutrient density in the diet. When done correctly (stop with the "Paleo" desserts and baked goods like they're health foods!) this way of eating has shown to be effective in reducing inflammation, normalizing blood lipids, and reducing body fat to healthy levels. As shown above, these are all things that will help raise serum zinc levels and normalize Zn:Cu ratios. 

Protein content and zinc absorption:

Both quantity and quality of protein is important here. There is a linear increase in zinc absorption with increased protein consumption. More so, consumption of animal protein (beef, eggs, cheese) has shown to increase the bioavailability of zinc in the diet (1). It has also shown to counteract the inhibitory effects of phytates in the diet. Unfortunately this is not true for soy protein isolates which contain a significant amount of phytic acid. 

Living like your ancestors is also of great importance. Mitochondrial DNA (mtDNA) mutations have played a huge role in your ancestral survival. The latitude in which your ancestors lived on, the sun they were exposed to, and food availability during the seasons all play a role in how your body functions. The 2017 Nobel Prize in Medicine confirmed that circadian rhythm affects the health every cell  in your body (both your cells and bacterial cells). Sleep is paramount, and sunlight controls when we sleep. Eating with the seasons and exposure to seasonal temperature extremes also will help the body better self regulate and handle daily stresses.  Regular exposure to unblocked sunlight during the day allows for proper hormone signalling and release. Regular exposure to blue dominant, artificial light, especially at night, can destroy important hormones, lipids, and neurotransmitters and inhibit proper hormonal signalling. 

Conclusion

Zinc is an essential element for life, both in plants and animals. It increases immunity and fights colds, acts as a powerful antioxidant that may help fight cancer, balances hormones, fights diabetes, maintains heart health by supporting blood vessels, prevents diarrhea, increases fertility, aids in nutrient absorption and digestion, supports liver health, and helps with muscle growth and repair. Following the advice in this post will help keep zinc levels optimal and lead to a healthier, more productive life.

Because supplementation has been shown to be effective in increasing serum zinc levels, head on over to the store and pick up some NightGainz for a full daily dose of zinc. 

(1) Bo Lönnerdal; Dietary Factors Influencing Zinc Absorption, The Journal of Nutrition, Volume 130, Issue 5, 1 May 2000, Pages 1378S–1383S, https://doi.org/10.1093/jn/130.5.1378S

(2) Palmiter, R. D. (1998). The elusive function of metallothioneins. Proceedings of the National Academy of Sciences of the United States of America, 95(15), 8428–8430.

(3) Marco Malavolta, et al; Metallothionein Downregulation in Very Old Age: A Phenomenon Associated with Cellular Senescence? Rejuvenation Research, Apr 2008, 455-459, http://doi.org/10.1089/rej.2008.0679

(4) E. Ehrenwald, G.M. Chisolm, P.L. Fox; Intact human ceruloplasmin oxidatively modifies low density lipoprotein, J. Clin. Invest., 93 (1994), pp. 1493-1501

(5) B. Bakhautdin, M. Febbraio, E. Goksoy, C.A.de la Motte, M.F. Gulen, E.P. Childers, S.L.Hazen, X. Li, P.L. Fox; Protective role of macrophage-derived ceruloplasmin in inflammatory bowel disease, Gut, 62 (2013), pp. 209-219

(6) Marco Malavolta, Francesco Piacenza, Andrea Basso, Robertina Giacconi, Laura Costarelli, Eugenio Mocchegiani; Serum copper to zinc ratio: Relationship with aging and health status; Mechanisms of Ageing and Development; Volume 151, 2015, Pages 93-100.

(7) U. Ravnskov; High cholesterol may protect against infections and atherosclerosis; QJM: An International Journal of Medicine, Volume 96, Issue 12, 1 December 2003, Pages 927–934.

(8) Solomons, N.W. & Jacob, R.A. & Pineda, O & Viteri, Fernando E. (1979). Studies on the bioavailability of zinc in man. II. Absorption of zinc from inorganic sources. The Journal of laboratory and clinical medicine. 94. 335-43.

(9) Hegenauer, J., Saltman, P., Ludwig, D., Ripley, L. & Ley, A. (1979) Iron-supplemented cow milk: identification and spectral properties of iron bound to casein micelles. J. Agri. Food Chem. 27:1294–1301.