The Singer-Nicolson Fluid-Mosaic Model of the cell’s lipid membrane is making scientific news again. The model, along with clinical evidence for the effectiveness of oral lipid replacement therapy (LRT), has recently been the subject of several peer review scientific papers. LRT is proving to be a valid method for restoring lipid membranes damaged by chronic infection and oxidative stress. New articles by Garth Nicolson, PhD and Michael Ash, DO, ND, BSc appear in Elsevier’s Biochimica et Biophysica Acta, and articles by Dr. Nicolson also appear in the newly Harvard-launched journal, Discoveries, as well as Alternative Therapies in Health and Medicine. Here, we summarize the clinical findings.
Cell membranes are dynamic, complex structures, fully integrated within tissues, and they are sensitive and reactive to environmental changes and signals. They have to quickly and selectively respond to disparate signals from within and outside cells. These subtle, dynamic and sensitive cellular structures continue to fascinate researchers who seek to uncover their secrets. LRT, the use of functional oral supplements containing cell membrane phospholipids and antioxidants, has been used to replace damaged, usually oxidized, membrane glycerophospholipids that accumulate during aging and in various adverse clinical conditions. Oral supplements can deliver therapeutic doses of membrane phospholipids as part of a daily supplement regimen, and oral membrane phospholipid supplements can be protected from oxidation, bile disruption and enzymatic digestion using protective fructooligosaccharides. This approach is nontoxic: LRT has been demonstrated to be safe in multiple analyses of acute and chronic toxicity. Importantly, none of these studies, which were mostly conducted in laboratory animals (mice, rats and rabbits), demonstrated any acute or chronic toxic effect, whether the lipids were given by oral, subcutaneous or intravenous administration. High doses of membrane phospholipids have also been given to humans with no apparent toxicity.
In animal studies, a special lipid preparation that mimics the ratios of phospholipids in the mitochondrial membrane prevented age-related declines in mitochondrial inner membrane potential and reduced the incidence of common mitochondrial DNA deletions found in aging rats. The effects were attributed to the ability of LRT to repair mitochondrial and other membranes and reduce the effects of oxidative damage on mitochondrial DNA.
Long-term administration of relatively high doses of LRT has actually improved cardiovascular blood markers. Thirty-five older (average age 60.7) individuals received over 2 grams per day of oral LRT and allied B Vitamins for over 6 months. Their cardiovascular blood marker levels, such as homocysteine, improved during the trial. Similarly, 58 patients with fatiguing illnesses received doses of 2 grams per day of oral LRT for 2 months; a followup showed that most of the individuals continued taking LRT on their own, seeing benefits in that fatigue and fatigue related symptoms declined significantly with no adverse effects.
There are numerous theories as to the multiple causes of aging, but one of the most significant is often forgotten in science reviews: inappropriate inflammation. This is referred to as “inflamm-aging.” LRT can help stabilize and even reverse this form of adverse aging. Inflamm-aging describes the close relationship between low-grade chronic innate immune system driven inflammation, both sterile and infection driven, and aging. The inflamm-aging process impairs cellular and mitochondrial housekeeping, leading to protein aggregation, mitochondrial DNA spillage and accumulation of dysfunctional mitochondria. Ultimately, this leads to loss in membrane fluidity and quality in mitochondria due to lipid peroxidation and associated decreased levels of cardiolipin, the primary phospholipid in the inner mitochondrial membrane. LRT can successfully reverse these age related changes.
Today, a version of the free radical theory of aging, focusing on mitochondria as source, as well as target of reactive oxygen species, is considered a valid theory to explain aging. During aging and chronic diseases oxidative damage to mitochondrial membranes, and their integrity impairs mitochondrial function.
For example, LRT used in older individuals (average age 72) has been shown to improve mitochondrial function, reduce fatigue and increase cognition. More impressively, the mitochondrial function of these individuals was restored to the same level of function as that displayed by a healthy 29 year-old control.
In other research, chronic fatigue syndrome patients present with evidence of oxidative damage to DNA and lipids, including markers of oxidized blood and membrane lipids. These patients also have sustained, elevated levels of peroxynitrite due to excess nitric oxide, which can also resultin lipid peroxidation and loss of mitochondrial function. LRT has been used in studies with severe chronic fatigued patients to reduce their fatigue and improve function. In a clinical trial of moderately fatigued patients there was good correspondence between reductions in fatigue and gains in mitochondrial function. After 8 weeks of LRT, mitochondrial function was significantly improved, and after 12 weeks of LRT, mitochondrial function was found to be similar to that found in young healthy adults. After twelve weeks of supplement use, individuals were placed on placebo without their knowledge for an additional 12 weeks, and their fatigue and mitochondrial function were again measured. Mitochondrial function was once again impaired, and fatigue had returned.
LRT has also been used in combination with other mitochondrial supplements to study long-term chronic illness patients with moderate to severe fatigue. These patients had been ill with intractable fatigue for an average of over 17 years, had been seen by many physicians (N15), and had taken an average of over 35 supplements and drugs with no effect on their fatigue. On the combination LRT, however, they responded with significant reductions in fatigue within 60 days. Regression analysis of the data indicated that reductions in fatigue were gradual, consistent, and occurred with a high degree of confidence.
LRT may also help restore gut function and eubiosis. Dysbiosis affects host susceptibility to metabolic disease, including obesity and diabetes as well as many other chronic illnesses. This is in part because mitochondria and gastrointestinal bacteria share certain patterns in their membranes. Both are of bacterial form, since even today mitochondria retain genetic traces of their former life as free living bacteria from aeons ago. A change in either is capable of triggering an intracellular inflammation switch known as the inflammasome – immunologists are currently exploring its role in multiple illnesses as it is a sensitive responder to both endogenous and exogenous triggers and represents a valid point of intervention for the management of chronic inflammation. LRT along with changes in diet can help restore eubiosis and reduce related sterile inflammation as well as remove oxidized phospholipids and oxidized cholesterol. For example; treatment of type 2 diabetic patients with oral LRT resulted in decreased serum triglyceride levels (37% reduction over 12 months) and reduced lipid peroxidation products compared to placebo. Other investigations show that membrane loss of mitochondrial DNA is stabilized by LRT and in such a situation reduces inflammasome activity. This presents a novel mechanism for management of gastrointestinal function.
Is LRT a lifestyle or lifelong supplement? More studies must be directed at determining if the positive clinical and biochemical changes brought about by the use of LRT actually cause long-term or only temporary changes. Since chronically fatigued patients slowly declined when LRT was discontinued, it may be that most chronic conditions require LRT as a lifelong requirement for good health and healthy aging.
