Nutri Focus

Selective Kinase Response Modulators (SKRMs)

The UK is facing a health crisis, an epidemic of our time, as imbalanced activity of the hormone insulin, which regulates blood sugars, is becoming more commonplace. The prevalence of what is called "Metabolic Syndrome" is rising at an alarming rate. In the UK it has been suggested that currently as much as 25% of the population show clear signs of this condition.

Metabolic Syndrome is characterised by a diagnosis of three or more of the following:

• Insulin resistance or glucose intolerance
• Elevated cholesterol
• High triglyceride levels
• Abdominal obesity (Elevated waist to hip ratio)
• High Blood Pressure
• Prothrombotic State (tendency towards blood clots)
• Pro-inflammatory state

Understanding more about how insulin dysfunction develops has led to revolutionary new solutions.

The role of inflammatory cytokines in insulin resistance

Dysfunction of the inflammatory response has been linked to insulin resistance. In one study it was demonstrated that the expression of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-a) in adipose tissue is significantly elevated in obese individuals; furthermore levels of expression of the cytokine correlated with the degree of hyperinsulinemia observed. Weight loss was shown to result in a decrease in the expression of TNF-a. TNF-a is thought to be implicated in insulin resistance through an inhibitory effect on signalling from insulin receptors. In obese rats, neutralisation of TNF-a results in increased insulin sensitivity in peripheral tissues.
An understanding of Kinases clarifies this link further...

Kinome and Kinases

It is now known that nutritional factors in the diet act as signalling molecules that interact with a comprehensive enzyme system known as the kinome. The human kinome is composed of the 540 known kinase enzymes plus many more as yet unidentified kinase's. This system of kinase enzymes is called the human kinome. The body relies on the kinome as a means of communicating signals from our environment (e.g., food, stress, toxin exposure) to the genome. It is well established that it is a combination of the environment we are exposed to and our genetic make-up that accounts for good or bad health: with the very latest kinome and kinase research we can begin to understand the processes that make this happen.
Kinases are the individual enzymes within the kinome that translate signal from molecules we consume, such as foods. They are capable of switching genes on or off; in fact they regulate the majority of cellular pathways. All kinase activity should be kept in balance in order to send the appropriate message to the genome.

GSK-3

One such kinase is Glycogen Synthase Kinase-3, or GSK-3, which is an enzyme that regulates glycogen synthesis in response to insulin. Unfortunately, GSK-3 activity can easily become upregulated as a result of eating unhealthy foods, ultimately leading to poor glucose utilisation and impaired signalling. In addition, GSK also triggers the activation of pro-inflammatory markers which further supports the link between insulin and inflammation.

• Inhibits insulin signalling
• Stimulates Nuclear factor - kappa b (NFk-b), which triggers the inflammatory response including TNF-a expression
• Promotes Apoptosis (cell death)
• Inhibits mitochondrial activity

SKRMs

Excitingly, new research is revealing that contain food components can selectively modify specific kinases in favour of healthy signalling. These components have been termed Selective Kinase Response Modulators (SKRMs).

Hops (Humulus Lupulus) and Acacia

Hops, the common name for Humulus Lupulus has been used for centuries; published literature indicates it has anti-inflammatory, anti-oxidant and anti-carcinogenic activity. Acacia has traditionally been used for various conditions including mouth inflammation, sore throat, colitis and diarrhoea. Ground breaking research has suggested a new role for these botanicals as selective modulators of the GSK-3 kinase response.

The Evidence

The functional Medicine Research Centre - the clinical research arm of Metagenics - has conducted a number of research studies relating to Acacia and Hops and their effects on insulin homeostasis. By supporting healthy kinase signalling, these SKRMs may help to maintain healthy blood sugar and triglyceride levels. In vitro testing has also demonstrated inhibition of IL-6 cytokines that influence insulin function. In addition, select combinations of hops and acacia have been clinically shown to improve fasting insulin and lipid parameters, both of which are risk factors for metabolic syndrome.

Clinical Research

In one study, participants were randomised to receive a combination supplement of reduced-iso-alpha acids (RIAA, from hops) and acacia extract or a placebo. The trial was conducted over 12 weeks and blood was taken at base line, 8 weeks and 12 weeks to assess the effect of supplementation on various parameters of metabolic syndrome. After 8 weeks, the active treatment group showed a greater decrease in fasting insulin and insulin levels two hours following consumption of a glucose solution, as compared to the controls; HOMA scores (homeostatic model assessment, estimating insulin sensitivity as a percentage of the reference population) also improved significantly compared to controls, as did triglyceride levels, indicating a role for SKRMs in maintaining insulin homeostasis in patients with metabolic syndrome.

In another randomised study patients with metabolic syndrome were eveluated for coronary risk markers. The really unique part of this study was that both the control and the intervention group received detailed dietary counselling on a low-GL diet with no calorific restriction, and were asked to complete 150 minutes per week of moderate exercise. Subjects in the intervention arm also received a soy-based metabolic food containing SKRMs from hops and acacia. Blood was drawn at baseline and 8 and 12 weeks and analysed for apoA1, apoB, and other CVD risk markers. This made it possible to see the effect of the supplementation in addition to what the diet and exercise programme alone can achieve. An just look what happened...

Powerful Results

A the end of the 12 weeks, both groups had experienced weight loss, despite no calorific restrictions. The intervention group, however, showed remarkably better overall results; persistent lowering effects on both apoB and the apoB/apoA1 ratio. The intervention arm also showed statistically greater reductions in lipid parameters - including the total cholesterol, HDL cholesterol, triglycerides, and the calculated LDL cholesterol - all risk factors for metabolic syndrome. In addition, this arm showed statistically greater reduction in serum homocysteine (another indicator of coronary artery disease) and a significant increase in HDL cholesterol. The research team chose to pay particular attention to apoB/apoA1 ratio because it is "the most powerful predictor out of all the routine risk factors that are available for coronary artery disease" and "significantly associated with metabolic syndrome".

Researchers concluded that the addition of a metabolic food containing SKRMs to a low-GL diet and exercise plan "significantly improves the apoB/apoA1 ratio, a major risk factor in subjects with metabolic syndrome".

The Future

This research opens up new possibilities for gaining control over the current pandemic of insulin dysfunction. Combined with the right dietary regime and nutritional support, SKRMs could revolutionise the treatment of insulin resistance.