Efforts to support healthy cardiovascular function are routinely pigeon-holed: take care of cholesterol to solve this problem, begin blood pressure medication to address that one. But there are such intricate connections between each area of cardiovascular focus that these types of regimens may not provide the whole-system cardiovascular support your patients are searching for.
Here, we will outline a method for diversifying supportive efforts and will include overviews of the physiology of cardiovascular health, the many connections within it, and the nutrients that may provide support for each.
Let’s begin with a discussion of a certain amino acid that greatly impacts cardiovascular health, despite the fact that many of our conversations about the system may not include mention of its name.
Homocysteine is a non-protein amino acid. Our bodies can recycle homocysteine into methionine or convert it to cysteine when aided by specific B vitamins. Homocysteine is biosynthesized from methionine, not taken into the body via nutrients in the diet. In the biosynthesis process, things get a bit complicated, beginning with methionine. First, it must receive an adenosine group from ATP (otherwise known as the energy molecule).
That reaction is catalyzed by S-adenosyl-methionine synthetase, a protein enzyme. SAM, or S-adenosylmethionine, is the product of that reaction. SAM transfers a methyl group to an acceptor molecule. At that point, hydrolysis occurs, yielding l-homocysteine, which can be then converted back into l-methionine or into l-cysteine.That’s a lot to take in, but the recycling process is a very important action in our bodies, and it’s important to understand if we are to understand homocysteine’s impact on health.
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When focusing on the conversion of homocysteine to lesser damaging metabolites, one needed look any further than three key nutrients. This process exists within very well established methylation biochemistry cycles including the Folate, Biopterin, Neurotransmitter and Homocysteine Cycles. When homocysteine enters this process, adequate B12 levels are necessary to stimulate the conversion to methionine. Trimethylglycine (TMG) is also required for this critical process. (Incidentally, upon the conversion of TMG to dimethylglycine [DMG], this newly formed glycine with two methyl donors drives the methylfolate cycle). From here methionine converts to SAMe which feeds the methylation pathways and supports numerous processes such as detoxification and mood. In losing its methyl group, SAMe becomes SAH (S−Adenosyl Homocysteine), which is then converted to homocysteine, at which point pyridoxine-linked enzymes involved in amino acid metabolism, specifically the cystathinione synthase enzyme, drive the conversion to cystathione and ultimiately to cysteine. This step becomes critical for cellular health when cysteine is combined with glutamate and glycine to form one of the body’s master nutrients, glutathione.
The recycling of this amino acid is instrumental to maintaining a healthy cardiovascular system. According to the National Institutes of Health Office of Dietary Supplements, “Elevated homocysteine levels are thought to promote thrombogenesis, impair endothelial vasomotor function, promote lipid peroxidation, and induce vascular smooth muscle proliferation” (“Dietary supplement fact sheet: vitamin B12 — health professional fact sheet,” 2011).
A high blood level of homocysteine, known as hyperhomocysteinemia, makes us more vulnerable to injury of the endothelial cells, which can lead to a compromise to blood vessels and, eventually long term implications. The coronary arteries supply the heart with necessary oxygenated blood. When that blood flow is blocked by plaque, the disease occurs. Some theories suggest that homocysteine may destroy endothelial cells, leading to the idea that plaque may attempt to fill in the damaged areas of the arteries once damage has occurred.
Other theories suggest that homocysteine may itself oxidize low-density lipoproteins, promoting buildup of cholesterol along the walls. Both theories, along with several others, describe reasoning for the correlation between arterial aging and elevated homocysteine levels. We aren’t sure, still, if high levels of homocysteine are independent risk factors for blood clots, strokes and heart attacks. But we are sure that high levels of homocysteine and cardiovascular health are linked, as are aging and increased homocysteine levels, making support for this aspect of the cardiovascular system ever more important for patients after the age of 40 (Wierzbicki, 2007).
Because homocysteine can drive the cholesterol’s deposit along the walls, homocysteine and blood pressure are also linked, indicating a need for a broad approach to cardiovascular system support. Also identified as potential underlying causes for the need for blood pressure support are elevated cortisol levels and nutrient depletion, often derived from medication.
Cortisol has quickly become a problematic hormone for numerous systems in the body when unchecked. And when there are elevated levels of cortisol in the blood, the pressure within the vascular system can be negatively impacted. One study performed by Litchfield and colleagues found elevated urinary free cortisol excretion in 153 white patients exhibiting essential hypertension than 18 normotensive controls.
The authors of the Four Corners Study published in 1992 observed 50 young people with high blood pressure and high parental blood pressure with higher plasma cortisol concentrations as compared with similar numbers of people with lower pressure. Morning plasma cortisol concentrations were elevated in untreated male hypertensives selected from the Paris Prospective Study (total cohort n = 6424) (Filipovsky et al, 1996). Interestingly enough, males have been implicated more than females when it comes to this correlation of higher cortisol levels and elevated blood pressure according to Walker et al (2000). The study examined 226 Swedish subjects in a cross-sectional study and found higher plasma cortisol was independently associated with higher diastolic blood pressure in men, but not women. This is far from conclusive that men are at greater risk, however, it highlights a commonly overlooked underlying risk factor for males exhibiting elevated blood pressure levels.
Another factor implicated in blood pressure impact is nutrient levels. In clinical practice it is quite common that patients present with a need for specific nutrient support, there are times when drug induced nutrient depletion is a driving factor. One such nutrient is Coenzyme Q10, often depleted with statin drugs as well as blood pressure medications. Both preliminary trials and double blind trials have concluded that supplementing with CoQ10 may lead to significant levels of support for blood pressure.
Much of the research has focused on doses of 100 mg/day for at least 2-3 months. (Folkers K, et al. Res Commun Chem Pathol Pharmacol 1984, Langsjoen P,et al. Mol Aspects Med 1994, Digiesi V, et al Molec Aspects Med 1994, Digiesi V, et al. Curr Ther Res 1990, Singh RB, et al. J Hum Hypertens 1999.) In fact, several studies have linked plasma homocysteine levels to blood pressure.
Observations of homocysteine- lowering therapies being followed by decreases in blood pressure may suggest that it’s possible for homocysteine’s role in blood pressure to be causal, but the evidence for mechanisms that can explain that relationship (homocysteine- induced arteriolar constriction, renal dysfunction and increased sodium reabsorption, and increased arterial stiffness) is still circumstantial. Therefore, while we know blood pressure and homocysteine are linked, we should consider a causal relationship as yet unproven (Stehouwer & Guldener, 2003). Certain health factors support healthy blood pressure, such as an abundance of vessel-specific nutrients, normal weight, structural integrity of the vessels, hormonal balance and a healthy stress response.
Cholesterol is among the most misunderstood and demonized physiologic components. It has many vital functions that indicate that it is far from the maniacal villain it has been painted as. In fact, it happens to be a foundational compound with structural roles as well as neuroendocrine. Cholesterol is an important component of the cell membranes, including organelle membranes inside the cell. The right proportion of phospholipids, fatty acids and cholesterol in cell membranes allows them to be flexible while still holding their shape and supports permeability.
When it comes to the supportive role it plays in vascular health and the structural support it provides to the tunica intima, it becomes clear that we’re not looking at an enemy but need to embrace cholesterol as a friend. As it has been stated in Know Your Fats, “Cholesterol is used by the body as raw material for the healing process. This is the reason the injured areas in the arteries have cholesterol along with several other components (such as calcium and collagen) in the “scar” tissue that is formed to heal the “wound”(Enig, Know Your Fats, 2000). Further, cholesterol is key in vitamin D synthesis via 7-dehydrocholesterol, which has the potential to provide support to the blood pressure, insulin resistance and the cardiac tissue itself (see Vitamin D Studies in subsequent section of this writing).
Beyond cardiovascular support, the endocrine system relies heavily on the production and distribution of adequate cholesterol. Adrenal and gonadal hormones are made from cholesterol. These are the stress handling, energy producing and reproductive hormones. (This explains the connection between elevated levels of stress and subsequent elevated serum cholesterol during prolonged stress.) From a digestive standpoint, cholesterol is converted into bile salts in the liver which are needed to break down and emulsify fats. Optimal levels of this function creates a cycle by which cholesterol is metabolized most effectively.
These processes are also driven by beneficial bacteria and thrive with adequate flora population in the gut (J Cardiovasc Dis Res. 2010 Oct-Dec; 1(4): 213–214). Based on the understanding relating to the multifaceted nature of cholesterol, functional elevation in the serum should lead to an exploration of the underlying cause for the elevation rather than strictly a ‘cholesterol lowering’ strategy.
One of the most significant findings in terms of B vitamins and homocysteine was actually brought to light through a meta-analysis of the clinical trials involving B6, folic acid and B12 relating to homocysteine levels.
Each piece of the cardiovascular system affects the others. The best way to support healthy levels of the three main components of cardiovascular health (homocysteine, blood pressure and cholesterol) is to diversify efforts, such that each component receives the nutrient support your patient’s body demands.